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Baskol G, Yetkin MÖ, Sevim DG, Guclu K, Arda H, Saracoglu H, Gahramanov K, Evereklioglu C. Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels are decreased in patients with Behçet's disease. Indian J Ophthalmol 2024; 72:S468-S472. [PMID: 38648454 PMCID: PMC467006 DOI: 10.4103/ijo.ijo_2829_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 12/30/2023] [Accepted: 01/02/2024] [Indexed: 04/25/2024] Open
Abstract
PURPOSE Behçet's disease (BD) is an autoimmune chronic systemic inflammatory disease characterized by a versatile clinical spectrum. Growth arrest specific protein 6 (GAS6)/soluble AXL (sAXL) signaling pathway draws attention in the resolution of inflammation, and its deficiency is associated with chronic inflammatory, autoimmune diseases, as well as clearance of apoptotic cells by phagocytes - efferocytosis. In this study, it was aimed to investigate whether GAS6/sAXL, interleukin (IL)-10, nitric oxide (NO), and BCL-2 levels were associated with inflammation and efferocytosis contributes to the pathogenesis of BD. METHODS A total of 37 Behçet patients with ocular involvement and 30 healthy control subjects were included in this study. GAS6, sAXL, IL-10, NO, and BCL-2 levels were quantified using enzyme-linked immunosorbent assay (ELISA) method. RESULTS Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels were significantly lower in patients with BD compared to the controls (P < 0.005, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). In correlation analysis, research parameters decreased in patients with BD was significantly correlated with each other: GAS6-IL-10 (r = 0.585, P < 0.001), GAS6-BCL-2 (r = 0.541, P < 0.001), sAXL-BCL-2 (r = 0.696, P < 0.001), IL-10-NO (r = 0.717, P < 0.001), IL-10-BCL-2 (r = 0.759, P < 0.001), and NO-BCL-2 (r = 0.541, P < 0.001). CONCLUSION In conclusion, decreased serum BCL-2 level may be an indicator of increased apoptosis in these patients and decreased levels of GAS6/sAXL, IL-10, and NO may indicate insufficient clearance of apoptotic bodies released as a result of increased apoptosis in BD patients.
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Affiliation(s)
- Gulden Baskol
- Department of Biochemistry, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Merve Ö. Yetkin
- Department of Biochemistry, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Duygu G Sevim
- Department of Ophthalmology, Division of Uvea-Behçet Unit, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Kenan Guclu
- Department of Biochemistry, Kayseri State Hospital, Kayseri, Turkey
| | - Hatice Arda
- Department of Ophthalmology, Division of Uvea-Behçet Unit, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Hatice Saracoglu
- Department of Biochemistry, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Kamran Gahramanov
- Department of Ophthalmology, Division of Uvea-Behçet Unit, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Cem Evereklioglu
- Department of Ophthalmology, Division of Uvea-Behçet Unit, Faculty of Medicine, Erciyes University, Kayseri, Turkey
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Arbrile M, Radin M, Medica D, Miraglia P, Rilat L, Cecchi I, Foddai SG, Barinotti A, Menegatti E, Roccatello D, Sciascia S. Finding the Needle in the Haystack: Serological and Urinary Biomarkers in Behçet's Disease: A Systematic Review. Int J Mol Sci 2023; 24:ijms24033041. [PMID: 36769366 PMCID: PMC9917563 DOI: 10.3390/ijms24033041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 02/08/2023] Open
Abstract
Urinary and serological markers play an essential role in the diagnostic process of autoimmune diseases. However, to date, specific and reliable biomarkers for diagnosing Behçet's disease (BD) are still lacking, negatively affecting the management of these patients. To analyze the currently available literature on serological and urinary BD biomarkers investigated in the last 25 years, we performed a systematic literature review using the Population, Intervention, Comparison, and Outcomes (PICO) strategy. One hundred eleven studies met the eligibility criteria (6301 BD patients, 5163 controls). Most of them were retrospective, while five (5%) were prospective. One hundred ten studies (99%) investigated serological biomarkers and only two (2%) focused on urinary biomarkers. One hundred three studies (93%) explored the diagnostic potential of the biomolecules, whereas sixty-two (56%) tested their effect on disease activity monitoring. Most articles reported an increase in inflammatory markers and pro-oxidant molecules, with a decrease in antioxidants. Promising results have been shown by the omics sciences, offering a more holistic approach. Despite the vast number of investigated markers, existing evidence indicates a persistent gap in BD diagnostic/prognostic indices. While new steps have been taken in the direction of pathogenesis and disease monitoring, international efforts for the search of a diagnostic marker for BD are still needed.
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Affiliation(s)
- Marta Arbrile
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
| | - Massimo Radin
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
- Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit, San Giovanni Bosco Hub Hospital, University of Turin, 10124 Turin, Italy
- Correspondence: ; Tel.: +39-3923741973
| | - Davide Medica
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
| | - Paolo Miraglia
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
| | - Letizia Rilat
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
| | - Irene Cecchi
- Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit, San Giovanni Bosco Hub Hospital, University of Turin, 10124 Turin, Italy
| | - Silvia Grazietta Foddai
- Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit, San Giovanni Bosco Hub Hospital, University of Turin, 10124 Turin, Italy
| | - Alice Barinotti
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
| | - Elisa Menegatti
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
- Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit, San Giovanni Bosco Hub Hospital, University of Turin, 10124 Turin, Italy
| | - Dario Roccatello
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
- Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit, San Giovanni Bosco Hub Hospital, University of Turin, 10124 Turin, Italy
| | - Savino Sciascia
- Department of Clinical and Biological Sciences, School of Specialization of Clinical Pathology, University of Turin, 10124 Turin, Italy
- Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit, San Giovanni Bosco Hub Hospital, University of Turin, 10124 Turin, Italy
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Omar HS, Taha FM, Fouad S, Ibrahim FA, El Gendy A, Bassyouni IH, El-Shazly R. The association between vitamin D levels and oxidative stress markers in Egyptian Behcet's disease patients. Orphanet J Rare Dis 2022; 17:264. [PMID: 35841050 PMCID: PMC9287946 DOI: 10.1186/s13023-022-02416-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 06/26/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Oxidative stress is postulated to have a major role in the pathophysiology of Bechet's Disease (BD). Growing evidence suggests that vitamin D has important roles in enhancing the expression of anti-inflammatory cytokines as well as certain antioxidants. However, there is little evidence currently about the antioxidant properties of vitamin D in BD. OBJECTIVE To study the relationship between vitamin D levels and the oxidative stress markers in patients with BD in addition to its association with disease activity and severity. METHODS Sixty BD patients (45 males, 15 females; mean age: 34.2 ± 9.6 years) were enrolled in this study and compared to a sex and age matched control group. Plasma 25-Hydroxy vitamin D (25-OH-D) was measured using Human (25-OH-D) ELISA assay. Plasma malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD) activity, catalase (CAT) activity and total antioxidant capacity (TAC) were determined by spectrophotometric methods in both groups. Plasma calcium (Ca) was measured by ELISA assay. RESULTS When compared to controls vitamin D, GSH, CAT activity, TAC and Ca were significantly lower in BD patients, while MDA and NO levels were significantly increased in BD patients. Our Results Found that vitamin D was inversely correlated to BD current Activity form (BDCAF), disease severity score, ESR, CRP, MDA and NO, while vitamin D was significantly positively correlated to GSH, SOD, TAC and Ca. CONCLUSION Our study confirms that a lower level of vitamin D is associated with the oxidative stress state in BD patients as detected by MDA and NO elevation as well as decreased GSH, SOD activity, CAT activity and TAC. Hence, Vitamin D fortified foods and beverages or supplementation may improve disease severity and oxidative stress in BD patients.
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Affiliation(s)
- Heba S Omar
- Medical Biochemistry and Molecular Biology Department, Kasr Al Ainy School of Medicine, Cairo University, Kasr Al Ainy St., El Manial, Cairo, 11562, Egypt.
| | - Fatma Mohamed Taha
- Medical Biochemistry and Molecular Biology Department, Kasr Al Ainy School of Medicine, Cairo University, Kasr Al Ainy St., El Manial, Cairo, 11562, Egypt
| | - Suzanne Fouad
- Nutrition and Food Science Department, National Research Centre, Dokki, Giza, 12622, Egypt
| | - Fatma A Ibrahim
- Biochemistry Department, National Research Centre, Dokki, Giza, 12622, Egypt
| | - Aliaa El Gendy
- Complementary Medicine Department, National Research Centre, Giza, 12622, Egypt
| | - Iman H Bassyouni
- Rheumatology and Rehabilitation Department, Kasr Alainy Hospitals, Cairo University, Kasr Al Ainy st., Cairo, Egypt
| | - Reem El-Shazly
- Rheumatology and Rehabilitation Department, Kasr Alainy Hospitals, Cairo University, Kasr Al Ainy st., Cairo, Egypt
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Kalenderoglu A, Yilmaz S, Oner RI, Orum MH, Karadag AS. Comparison of nitric oxide level in Behçet’s disease patients with or without psychiatric comorbidity. J Immunoassay Immunochem 2019; 40:502-514. [DOI: 10.1080/15321819.2019.1646659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Aysun Kalenderoglu
- Department of Psychiatry, Adiyaman University Faculty of Medicine, Adiyaman, Turkey
| | - Sedat Yilmaz
- Department of Biochemistry, Adiyaman University Faculty of Medicine, Adiyaman, Turkey
| | - Ramazan Ilyas Oner
- Department of Internal Medicine, Adiyaman University Faculty of Medicine, Adiyaman, Turkey
| | | | - Ayse Sevgi Karadag
- Department of Ophthalmology, Adiyaman University Faculty of Medicine, Adiyaman, Turkey
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Muhammad JS, Ishaq M, Ahmed K. Genetics and Epigenetics Mechanism in the Pathogenesis of Behçet's Disease. Curr Rheumatol Rev 2019; 15:7-13. [PMID: 29779484 DOI: 10.2174/1573397114666180521090335] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 04/20/2018] [Accepted: 05/13/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Behçet's Disease (BD) is characterized by numerous systemic manifestations and is known for its ability to affect both, arteries and the veins. However, the etiology of BD is only partially understood, and previous studies have demonstrated a role for genetic and epigenetic factors that contribute to disease pathophysiology. Several studies have implicated T cells and monocytes in the pathogenesis of BD especially when these cells are stimulated by heat shock proteins and streptococcal antigen. Furthermore, during disease exacerbations adenosine deaminase has an important role in activating lymphocyte proliferation, maturation, and differentiation in BD. This article presents a review of the published literature mainly from the last 20 years. The topics of main concern were the role of genetic and epigenetic factors as contributing factors in disease pathophysiology. RESULT AND CONCLUSION The authors used MeSH terms "Behçet's disease" with "pathophysiology," "pathogenesis," "genetic" or "epigenetic" to search the PubMed database. All the relevant studies identified were included and are described according to the aforementioned subheadings.
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Affiliation(s)
- Jibran Sualeh Muhammad
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Muhammad Ishaq
- Department of Internal Medicine, Jinnah Medical College Hospital, Korangi, Karachi, Pakistan
| | - Khalid Ahmed
- Department of Biological and Biomedical Sciences, the Aga Khan University Hospital, Karachi, Pakistan
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Djaballah-Ider F, Djeraba Z, Chemli M, Dammene-Debbihe N, Lounis D, Belguendouz H, Medour Y, Chaib S, Touil-Boukoffa C. Influence of corticosteroid therapy on IL-18 and nitric oxide production during Behçet's disease. Inflammopharmacology 2018; 26:725-735. [PMID: 29600486 DOI: 10.1007/s10787-018-0472-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 03/23/2018] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND AIMS Behçet's disease (BD) is a chronic multisystemic inflammatory disease with complex etiopathogenesis. Th1-proinflammatory cytokines seem to be involved in its pathogenesis. Our current study aims to evaluate interleukin-18 (IL-18) and nitric oxide (NO) involvement in the development of different clinical manifestations of BD as well as to investigate the corticosteroid therapy effect on this production in Algerian patients. METHODS For this purpose, we evaluated in vivo and ex vivo IL-18, interferon-γ (IFN-γ) levels using ELISA and NO production by the Griess' method in naïve-active and corticosteroid-treated BD patients with different clinical manifestations. Additionally, we assessed CD40/CD40L expression by flow cytometrics assay in these groups of patients. RESULTS AND DISCUSSION Our results indicate that IL-18 and nitrite levels were higher in naïve-active BD patients. Interestingly, this high production differed according to the clinical manifestations and was associated with an increased risk of mucocutaneous and vascular involvement. Concerning corticosteroid treated-active BD patients, no difference was observed in this production between each clinical subgroup. However, IFN-γ levels increased in all categories of active patients. Interestingly, corticosteroid therapy reduced significantly these inflammatory mediators regardless of the clinical manifestations studied. In addition, the CD40/CD40L expression differed according to the clinical presentations. CONCLUSION Collectively, our results suggest that concomitant high production of IL-18 and NO in naïve-active BD patients is related to an increased risk of mucocutaneous lesions and vascular involvement. Moreover, the relationship between these two inflammatory markers could constitute a predictable tool of BD clinical presentations and an early factor of therapy efficiency.
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Affiliation(s)
| | - Zineb Djeraba
- Universite des Sciences et de la Technologie Houari Boumediene, Algiers, Algeria
| | - Mourad Chemli
- Service de Medecine Interne, Hopital Dr Md Seghir NEKKACHE, Algiers, Algeria
| | | | - Doulkifly Lounis
- Service de Medecine Interne, Hopital Dr Md Seghir NEKKACHE, Algiers, Algeria
| | - Houda Belguendouz
- Universite des Sciences et de la Technologie Houari Boumediene, Algiers, Algeria
| | - Yanis Medour
- Service d'Immunologie, Hopital Dr Md Seghir NEKKACHE, Algiers, Algeria
| | - Samia Chaib
- Service d'Immunologie, Hopital Dr Md Seghir NEKKACHE, Algiers, Algeria
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Masullo LF, Magalhães RA, Lemes RPG, de Almeida Filho TP, de Castro MF, Maia Filho PA, Cunha TOV, Quidute ARP, Fontenele EGP, Sun G, Martins MRA. Levothyroxine Replacement Improves Oxidative Status in Primary Hypothyroidism. Front Endocrinol (Lausanne) 2018; 9:655. [PMID: 30467493 PMCID: PMC6235903 DOI: 10.3389/fendo.2018.00655] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 10/19/2018] [Indexed: 12/11/2022] Open
Abstract
Objective: Although hypothyroidism has been linked to oxidative stress, data regarding the relationship between thyroid hormone levels and oxidative stress is still inconsistent. This study was designed to evaluate the effect of levothyroxine replacement on oxidative stress in women with primary hypothyroidism. Design: A total of 25 female patients with primary hypothyroidism were included. Oxidative stress markers were measured before and after levothyroxine replacement treatment in all patients. Methods: Oxidative stress was evaluated through the measurement of oxidants (thiobarbituric acid reactive substances [TBARS] and nitrite/nitrate levels), and antioxidants (superoxide dismutase and catalase activity). Results: Antioxidant catalase activity (63.77 ± 23.8 vs. 50.12 ±12.75 atv/min; p = 0.03) was significantly increased and the levels of TBARS (3.02 ± 0.86 vs. 3.55 ± 0.87 μM; p = 0.03) were significantly decreased in the state of euthyroidism after levothyroxine replacement compared to the hypothyroidism before levothyroxine treatment. No significant change in neither nitrite/nitrate concentration (p = 0.18) nor in superoxide dismutase activity (p = 0.93) after L-T4 adjustment was found. Conclusions: Our data demonstrate that levothyroxine replacement improved oxidative status in patients with primary hypothyroidism, indexed by the significantly decreased levels of malonaldehyde (MDA) and increased catalase (CAT) activity.
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Affiliation(s)
- Laís Farias Masullo
- Research Laboratory in Haemoglobinopathies and Genetics of Haematological Diseases, Federal University of Ceará, Fortaleza, Brazil
- Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Brazil
| | - Rejane Araújo Magalhães
- Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Brazil
- Division of Endocrinology and Diabetes, Hospital Universitário Walter Cantídio, Federal University of Ceará, Fortaleza, Brazil
| | - Romélia Pinheiro Gonçalves Lemes
- Research Laboratory in Haemoglobinopathies and Genetics of Haematological Diseases, Federal University of Ceará, Fortaleza, Brazil
- Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Brazil
| | - Tarcísio Paulo de Almeida Filho
- Research Laboratory in Haemoglobinopathies and Genetics of Haematological Diseases, Federal University of Ceará, Fortaleza, Brazil
- Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Brazil
| | - Marilena Facundo de Castro
- Research Laboratory in Haemoglobinopathies and Genetics of Haematological Diseases, Federal University of Ceará, Fortaleza, Brazil
| | - Pedro Aurio Maia Filho
- Research Laboratory in Haemoglobinopathies and Genetics of Haematological Diseases, Federal University of Ceará, Fortaleza, Brazil
- Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Brazil
| | | | - Ana Rosa Pinto Quidute
- Division of Endocrinology and Diabetes, Hospital Universitário Walter Cantídio, Federal University of Ceará, Fortaleza, Brazil
- Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil
- Drug Research and Development Center-NPDM/Fortaleza, Fortaleza, Brazil
| | - Eveline Gadelha Pereira Fontenele
- Division of Endocrinology and Diabetes, Hospital Universitário Walter Cantídio, Federal University of Ceará, Fortaleza, Brazil
- Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Brazil
| | - Guang Sun
- Discipline of Medicine, Faculty of Medicine, Memorial University, St John's, NL, Canada
| | - Manoel Ricardo Alves Martins
- Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Brazil
- Division of Endocrinology and Diabetes, Hospital Universitário Walter Cantídio, Federal University of Ceará, Fortaleza, Brazil
- Drug Research and Development Center-NPDM/Fortaleza, Fortaleza, Brazil
- Department of Clinical Medicine, Federal University of Ceará, Fortaleza, Brazil
- *Correspondence: Manoel Ricardo Alves Martins
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Djeraba Z, Benlabidi F, Djaballah-Ider FZ, Medjeber O, Arroul-Lammali A, Belguendouz H, Otmani F, Touil-Boukoffa C. Vitamin D status in Algerian Behçet’s disease patients: an immunomodulatory effect on NO pathway. Immunopharmacol Immunotoxicol 2017; 39:243-250. [DOI: 10.1080/08923973.2017.1327967] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Affiliation(s)
- Zineb Djeraba
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Biological Sciences Faculty, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
| | - Fatiha Benlabidi
- Internal Medicine Service at Mustapha Bacha Hospital, Algiers, Algeria
| | - Fatma Zohra Djaballah-Ider
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Biological Sciences Faculty, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
| | - Oussama Medjeber
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Biological Sciences Faculty, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
| | - Amina Arroul-Lammali
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Biological Sciences Faculty, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
| | - Houda Belguendouz
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Biological Sciences Faculty, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
| | - Fifi Otmani
- Internal Medicine Service at Mustapha Bacha Hospital, Algiers, Algeria
| | - Chafia Touil-Boukoffa
- Cytokines and NO Synthases Team, Laboratory of Cellular and Molecular Biology (LBCM), Biological Sciences Faculty, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria
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Yuksel M, Yildiz A, Oylumlu M, Turkcu FM, Bilik MZ, Ekinci A, Elbey B, Tekbas E, Alan S. Novel markers of endothelial dysfunction and inflammation in Behçet’s disease patients with ocular involvement: epicardial fat thickness, carotid intima media thickness, serum ADMA level, and neutrophil-to-lymphocyte ratio. Clin Rheumatol 2015; 35:701-8. [DOI: 10.1007/s10067-015-2907-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2015] [Revised: 02/13/2015] [Accepted: 02/18/2015] [Indexed: 12/30/2022]
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Cytokines Modulate the "Immune-Metabolism" Interactions during Behçet Disease: Effect on Arginine Metabolism. Int J Inflam 2015; 2015:241738. [PMID: 25692069 PMCID: PMC4322663 DOI: 10.1155/2015/241738] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 09/15/2014] [Accepted: 11/04/2014] [Indexed: 11/18/2022] Open
Abstract
Aim and Methods. In this study, we evaluated NOS and arginase activities and their regulation during Behçet disease, a systemic chronic inflammatory disorder with uncertain etiology. The peripheral blood mononuclear cells of 36 patients and 15 control samples (PBMC) were cultured in either RPMI 1640, MEM, or DMEM complemented with 10% of FBS and antibiotics. Cultures were performed with or without the control or patients plasma. Subsequent treatment contained anticytokines (IL-6, TGF-β), a mitogenic effector (PHA), or NOS modulators (L-NMMA, BH4). Culture supernatants were harvested after 24 h of incubation. NO and urea measurements were, respectively, performed by modified Griess and Berthelot methods. Results. Higher urea levels were found in patients' plasma compared to the control's (P < 0.05). NOS modulators induced inverted production profiles for NO and urea (P < 0.05). Their results differed depending on the clinical findings (P < 0.05). It was also found that cytokine neutralization induced different response profiles in patients as opposed to control cultures (P < 0.05). Conclusion. Our results suggest that arginases can compete with NOS2 for L-arginine during Behçet disease. Both enzymes are regulated by environmental cytokines and substrate availability. Furthermore, it seems that NOS/arginase balance is dependent on clinical expression.
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Mazzoccoli G, Matarangolo A, Rubino R, Inglese M, De Cata A. Behçet syndrome: from pathogenesis to novel therapies. Clin Exp Med 2014; 16:1-12. [PMID: 25447032 DOI: 10.1007/s10238-014-0328-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Accepted: 11/22/2014] [Indexed: 12/11/2022]
Abstract
Behçet syndrome is a chronic disease hallmarked by inflammation of the blood vessels that is related to an autoimmune reaction caused by inherited susceptibility due to specific genes and environmental factors, probably components of infectious microorganisms, which turn on or get going the disease in genetically susceptible subjects. The more common clinical expression of the disease is represented by a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis, sometimes associated with inflammatory arthritis, phlebitis, iritis, as well as inflammation of the digestive tract, brain, and spinal cord. The treatment strategies used to manage the manifestations of Behçet syndrome have gradually progressed, and a number of new therapeutic resources have been implemented in recent years, allowing better control of pathogenic mechanisms, reducing symptoms and suffering, and ameliorating patient's outcome.
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Affiliation(s)
- Gianluigi Mazzoccoli
- Division of Internal Medicine and Chronobiology Unit, Department of Medical Sciences, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
| | - Angela Matarangolo
- Division of Internal Medicine and Rheumatology Unit, Department of Medical Sciences, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy
| | - Rosa Rubino
- Division of Internal Medicine and Chronobiology Unit, Department of Medical Sciences, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy
| | - Michele Inglese
- Division of Internal Medicine and Rheumatology Unit, Department of Medical Sciences, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy
| | - Angelo De Cata
- Division of Internal Medicine and Rheumatology Unit, Department of Medical Sciences, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.
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Talaat RM, Ashour ME, Bassyouni IH, Raouf AA. Polymorphisms of interleukin 6 and interleukin 10 in Egyptian people with Behcet's disease. Immunobiology 2014; 219:573-582. [PMID: 24703990 DOI: 10.1016/j.imbio.2014.03.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2013] [Revised: 01/24/2014] [Accepted: 03/12/2014] [Indexed: 12/31/2022]
Abstract
Cytokines play critical roles in the pathogenesis of Behçet's disease (BD). They mediated many of the effectors and regulatory functions of immune and inflammatory responses. Many studies have linked Interleukin-6 (IL-6) and Interleukin-10 (IL-10) pathologically to BD. Thus, this study aimed to investigate the associations between IL-6 and IL-10 promoter single-nucleotide polymorphisms (SNPs) and the susceptibility to BD and their implication on plasma levels. We genotyped IL-6 -174 G/C (rs1800795) using Mutagenically Separated Polymerase Chain Reaction PCR (MS-PCR) and IL-10 -1082 G/A (rs1800896) and -819 C/T (rs1800871) using Sequence Specific Primer PCR (SSP-PCR) in 87 Egyptian patients and 97 controls. The plasma levels of IL-6 and IL-10 were measured using Enzyme-linked Immunosorbent Assay (ELISA). Significant increase in the frequency of -1082 GG genotype (P<0.05, OR=2.25, 95%CI=1.03-4.91) and significant decrease in the frequency of -1082 GA genotype (P<0.05, OR=0.53, 95%CI=0.29-0.96) was demonstrated in BD patients compare to controls. Patients with genital ulcer had significantly lower frequency of -1082 GG (P<0.05, OR 0.2, 95% CI=0.04-0.99) and G allele (P<0.05, OR=0.28, 95%CI=0.08-0.93), while patients with ocular manifestations had significantly higher frequency of -1082 G allele (P<0.01, OR=2.28, 95%CI=1.19-4.36). BD patients had significantly higher level of IL-6 (P<0.001) and significantly lower level of IL-10 (P<0.001) compared to controls. The changes in the level of cytokines were independent of any genotype of IL-6 or any genotype/haplotype of IL-10. Patients with active disease state had significantly higher level of IL-6 compared to patients in remission (P<0.05). In conclusion, our preliminary study indicates that the polymorphism at IL-10 -1082 G/A may play a role in BD susceptibility. The significant increase in IL-6 level and the significant decrease in IL-10 level in BD patients were independent of any particular genotype in IL-6 or any particular genotype/haplotype in IL-10.
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Affiliation(s)
- Roba M Talaat
- Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt.
| | - Mohamed E Ashour
- Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Egypt; Center of Genomics, Helmy Institute, Zewail City of Science and Technology, Giza, Egypt
| | - Iman H Bassyouni
- Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed A Raouf
- National Liver Institute (NLI), Menufia University, Egypt
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Yildirim M, Baysal V, Inaloz HS, Doguc D. The Significance of Serum Nitric Oxide Levels in Behçet's Disease and Recurrent Aphthous Stomatitis. J Dermatol 2014; 31:983-8. [PMID: 15801262 DOI: 10.1111/j.1346-8138.2004.tb00641.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Behçet's disease (BD) is an inflammatory multisystem disorder characterized by recurrent oral and genital aphthous ulcers, arthritis, uveitis, and thrombophlebitis; it can involve several organs. However, recurrent aphthous stomatitis (RAS) can be seen without a confirmed diagnosis of BD. Moreover, there is no way of predicting whether a patient with RAS will develop BD. Nitric oxide (NO) is a free radical synthesized from L-arginine by one of the family of nitric oxide synthase (NOS) enzymes. Increased production of NO during several inflammatory and infectious processes has been recently postulated. Our aim was to investigate the serum NO levels in patients with active and inactive BD and RAS. Forty-six patients with BD, 30 patients with RAS and 30 healthy controls were enrolled in the study. The patients with BD were separated into two groups: clinically active (n = 24) and inactive (n = 22). A blood sample was collected from all subjects in order to determine their serum NO levels. In patients with active BD, higher serum levels of NO metabolite were found in comparison with patients with inactive BD, in patients with RAS, or healthy controls (p < 0.05). We also found higher serum NO metabolite levels in patients with RAS than in healthy controls (p < 0.05). In patients with inactive BD, statistically significant higher levels of serum NO levels were found in comparison with the control group (p < 0.05). However, we found no statistically significant difference between the patients with inactive BD and RAS, which indicated that inactive BD cannot be distinguished from RAS by serum NO levels. We conclude that serum NO levels may be an important marker for estimating the severity of BD. However, further studies are needed to confirm our findings.
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Affiliation(s)
- Mehmet Yildirim
- University of Suleyman Demirel, School of Medicine, Department of Dermatology, Isparta, Turkey
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Hatemi G, Merkel PA, Hamuryudan V, Boers M, Direskeneli H, Aydin SZ, Yazici H. Outcome measures used in clinical trials for Behçet syndrome: a systematic review. J Rheumatol 2014; 41:599-612. [PMID: 24488418 DOI: 10.3899/jrheum.131249] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Behçet syndrome (BS) is a multisystem vasculitis that is most active during young adulthood, causing serious disability and significant impairment in quality of life. Differences in the disease course, severity, and organ involvement between patients, depending on the age at presentation and sex, makes it impossible to determine a single management strategy. The diversity and variability in the outcome measures used in clinical trials in BS makes it difficult to compare the results or inform physicians about the best management strategy for individual patients. There is a large unmet need to determine or develop validated outcome measures for use in clinical trials in BS that are acceptable to researchers and regulatory agencies. We conducted a systematic review to describe the outcomes and outcome measures that have been used in clinical trials in BS. This review revealed the diversity and variability in the outcomes and outcome measures and the lack of standard definitions for most outcomes and rarity of validated outcome tools for disease assessment in BS. This systematic literature review will identify domains and candidate instruments for use in a Delphi exercise, the next step in the development of a core set of outcome measures that are properly validated and widely accepted by the collaboration of researchers from many different regions of the world and from different specialties, including rheumatology, ophthalmology, dermatology, gastroenterology, and neurology.
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Affiliation(s)
- Gulen Hatemi
- From the Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey; Division of Rheumatology and Department of Epidemiology, University of Pennsylvania, Philadelphia, PA, USA; Department of Clinical Epidemiology, VU University Medical Center, Amsterdam, The Netherlands; Department of Rheumatology, Marmara University School of Medicine, Istanbul; Department of Rheumatology, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul, Turkey
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Rapaport MJ, Rapaport V. The red skin syndromes: corticosteroid addiction and withdrawal. ACTA ACUST UNITED AC 2014. [DOI: 10.1586/17469872.1.4.547] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Djeraba Z, Boumedine K, Arroul-Lammali A, Otmani F, Belguendouz H, Touil-Boukoffa C. Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet's disease: a study in Algerian patients. Immunopharmacol Immunotoxicol 2013; 36:78-86. [PMID: 24369064 DOI: 10.3109/08923973.2013.873048] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet's disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD.
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Affiliation(s)
- Zineb Djeraba
- USTHB (University of Sciences and Technology), Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Science , Algiers , Algeria and
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Balta S, Balta I, Demirkol S, Ozturk C, Demir M. Endothelial Function and Behçet Disease. Angiology 2013; 65:657-9. [DOI: 10.1177/0003319713513146] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Sevket Balta
- Department of Cardiology, Eskisehir Military Hospital, Eskişehir, Turkey
| | - Ilknur Balta
- Department of Dermatology, Kecioren Training and Research Hospital Ankara, Turkey
| | - Sait Demirkol
- Department of Cardiology, Gulhane Medical Academy Ankara, Turkey
| | - Cengiz Ozturk
- Department of Cardiology, Gulhane Medical Academy Ankara, Turkey
| | - Mustafa Demir
- Department of Cardiology, Gulhane Medical Academy Ankara, Turkey
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Bozkurt M, Yüksel H, Em S, Oktayoglu P, Yildiz M, Akdeniz D, Nas K. Serum prolidase enzyme activity and oxidative status in patients with Behçet's disease. Redox Rep 2013; 19:59-64. [PMID: 24225260 DOI: 10.1179/1351000213y.0000000072] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
OBJECTIVES To assess serum prolidase enzyme activity and oxidative stress in patients with Behçet's disease (BD). METHODS The study population consisted of BD patients (n = 42) and healthy participants (n = 29). BD patients were classified as active (n = 18) or inactive (n = 24) according to disease activity. Serum prolidase enzyme activity, total antioxidant status (TAS), total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA) levels were measured. RESULTS In BD patients with active disease, serum prolidase activity was significantly higher compared with the inactive and control participants. Serum prolidase activity was also significantly higher in all BD patients in comparison with controls. Serum prolidase activity was also positively correlated with OSI, C-reactive protein, and active BD. MDA, TOS, and OSI levels were all significantly higher in the BD group when compared with the healthy control participants. Serum TAS levels were significantly lower in BD patients in comparison with healthy controls. CONCLUSION High prolidase activity may indicate critical biological activities relevant to pathological events in BD, and this activity may be a biological indicator of disease. Further studies are needed to verify these findings.
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Akcay YD, Sagin FG, Aksu K, Keser G, Taylor E, Knight I, Winyard PG, Sozmen EY. A panel of oxidative stress assays does not provide supplementary diagnostic information in Behcet's disease patients. JOURNAL OF INFLAMMATION-LONDON 2012; 9:13. [PMID: 22472022 PMCID: PMC3348053 DOI: 10.1186/1476-9255-9-13] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/06/2011] [Accepted: 04/03/2012] [Indexed: 11/10/2022]
Abstract
Background Recent findings suggest a role of oxidative stress in the pathogenesis of Behcet's disease (BD), but the utility of oxidative stress-associated assays in offering diagnostic information or in the monitoring of disease activity is largely unassessed. Objective and methods We aimed to measure oxidative and inflammatory markers, along with the markers of reactive nitrogen species, S-nitrosothiols and 3-nitrotyrosine, in BD patients (n = 100) and healthy volunteers (n = 50). These markers were evaluated in regard to their role in the pathogenesis of BD as well as their relation to clinical presentation, disease activity and duration. Results Median values for erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, and IL-18 levels, as well as myeloperoxidase (MPO) activity, were statistically higher in the patient group compared to controls. Some inflammation markers (ESR, neutrophil and leukocyte counts) were statistically higher (p < 0.05) in the active period. In contrast, oxidative stress-associated measures (erythrocyte lipid peroxidation, antioxidant enzymes and measures of serum antioxidant capacity), revealed no statistically significant differences between the median values in BD patients versus healthy control subjects (p > 0.05 in all statistical comparisons), nor was there any difference in median levels of these oxidative stress markers in active disease versus disease remission. S-nitrosothiols and 3-nitrotyrosine were undetectable in BD plasma. Conclusions The application of oxidative stress-associated measures to BD blood samples offered no supplemental diagnostic or disease activity information to that provided by standard laboratory measures of inflammation. S-nitrosothiols and 3-nitrotyrosine appeared not to be markers for active BD; thus the search for biochemical markers that will indicate the active period should be continued with larger studies.
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Affiliation(s)
- Yasemin D Akcay
- Department of Biochemistry, Ege University, School of Medicine, 35100 Bornova, Izmir, Turkey.
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García-Palenzuela R, Graña Gil J, Varela Arias M, Tovar Bobo M. Actualización de la enfermedad de Behçet. A propósito de 2 casos en atención primaria. Semergen 2012. [DOI: 10.1016/j.semerg.2011.07.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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Abstract
PURPOSE OF REVIEW To alert physician to timely recognition and current treatment of recurrent hypopyon iridocyclitis or panuveitis in ocular Behçet disease (OBD). RECENT FINDINGS Interferon-α, rituximab, intravitreal triamcinolone, and biological response modifiers by tumor necrosis factor inhibitors such as infliximab and adalimumab are being used increasingly for the treatment of severe sight-threatening ocular inflammation including retinal vasculitis and cystoid macular edema (CME). SUMMARY Biological agents offer tremendous potential in the treatment of OBD. Given that OBD predominantly afflicts the younger adults in their most productive years, dermatologist, rheumatologist, internist, or general practitioners supervising patients with oculo-articulo-oromucocutaneous syndromes should be aware of systemic Behçet disease. Early recognition of ocular involvement is important and such patients should strongly be instructed to visit immediately an ophthalmologist, as uveitis management differs from extraocular involvements with high ocular morbidity from sight-threatening complications due to relapsing inflammatory attacks in the posterior segment of the eye. A single infliximab infusion should be considered for the control of acute panuveitis, whereas repeated long-term infliximab infusions were proved to be more effective in reducing the number of episodes in refractory uveoretinitis with faster regression and complete remission of CME.
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Affiliation(s)
- Cem Evereklioglu
- Department of Ophthalmology, Erciyes University Medical Faculty, Kayseri, Turkey
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Pineton de Chambrun M, Wechsler B, Geri G, Cacoub P, Saadoun D. New insights into the pathogenesis of Behçet's disease. Autoimmun Rev 2011; 11:687-98. [PMID: 22197900 DOI: 10.1016/j.autrev.2011.11.026] [Citation(s) in RCA: 199] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2011] [Accepted: 11/27/2011] [Indexed: 01/01/2023]
Abstract
Behçet's disease (BD) is a recurrent systemic inflammatory disorder of unknown origin characterized by oral and genital mucous ulcer, uveitis, and skin lesions. Involvement of large vessels, central nervous system (CNS), gastrointestinal tract and thrombotic events are less frequent but can be life threatening. The aim of this review is to provide new insights into the pathogenesis of BD. Over the past year substantial advances have been done in the understanding of the genetic [1,2] and immunology [3] of BD. BD is at the crossroad between autoimmune and autoinflammatory syndromes. In common with autoimmune diseases BD shares class I MHC association. However, in contrast to autoimmune disorders, BD has clinical features that seem to be mostly autoinflammatory. The pathogenesis of BD is still unknown, but major determinants of the genetic and immune system abnormalities have been reported recently. Triggering infectious factors are supposed to participate in the outbreak of BD in genetically predisposed patients. Two recent large genome-wide association study (GWAS) conducted in Turkey and Japan reported association between single nucleotide polymorphism (SNP) of interleukin (IL)-10 and IL-23R/IL-12RB2 genes and BD. New insights into the perturbations of T cell homeostasis of BD recently emerged. We have recently demonstrated the promotion of Th17 responses and the suppression of regulatory T cells (Tregs) that were driven by interleukin (IL)-21 production and that correlates with BD activity. Inflammatory cells within BD inflammatory lesions included mostly neutrophils, Th1 and Th17 cells, and cytotoxic CD8+ and γδ T cells. Altogether, the recent progresses in the knowledge of BD pathogenesis pave the way for innovative therapy.
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Affiliation(s)
- Marc Pineton de Chambrun
- Department of Internal Medicine and Laboratory I3 Immunology, Immunopathology, Immunotherapy, UMR CNRS 7211, INSERM U959, Groupe Hospitalier La Pitié-Salpetrière, Université Pierre et Marie Curie, Paris 6, Paris, France
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Messaoudene D, Belguendouz H, Ahmedi ML, Benabdekader T, Otmani F, Terahi M, Youinou P, Touil-Boukoffa C. Ex vivo effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production in Algerian patients with Adamantiades-Behçet's disease. JOURNAL OF INFLAMMATION-LONDON 2011; 8:35. [PMID: 22104639 PMCID: PMC3248364 DOI: 10.1186/1476-9255-8-35] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/16/2011] [Accepted: 11/21/2011] [Indexed: 11/10/2022]
Abstract
Background Adamantiades-Behçet's disease (ABD) is a chronic multisystemic inflammation with unknown pathophysiology. This disorder is associated with a dysregulation of the cytokine network that hyperactivates neutrophils and macrophages. In this study, we investigate the modulatory effects of flavonoïd compounds extracted from Algerian medicinal plant Artemisia herba alba on Th1 and Th2 cytokines and nitric oxide production. Methods The modulatory effects of flavonoïds extracted from Artemisia herba alba on cytokines and nitric oxide production by peripheral blood mononuclear cells isolated from Algerian ABD patients and healthy controls were respectively measured by means of ELISA assays and Griess modified method. Results Our results show that flavonoïds significantly reduce the production of interleukin-12, the key effector of T helper 1 (Th1) cells and nitric oxide in a dose-dependent manner in Adamantiades-Behçet's disease. In contrast, the production of IL-4, the key marker of Th2 cells was increased. Conclusion This study suggests that in vitro supplementation with flavonoïds extracted from Artemisia herba alba could have potential immuno-modulatory effects characterised by a down-regulation and up-regulation of Th1 and Th2 cytokines, respectively. Moreover, flavonoïds may prevent nitric oxide induced damages.
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Affiliation(s)
- Djamel Messaoudene
- Laboratoire de Biologie Cellulaire et Moléculaire (LBCM), FSB, USTHB, Université de Bab-Ezzouar, BP32, 16111, Algiers, Algeria.
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Erdurmuş M, Yağcı R, Atış Ö, Karadağ R, Akbaş A, Hepşen IF. Antioxidant status and oxidative stress in primary open angle glaucoma and pseudoexfoliative glaucoma. Curr Eye Res 2011; 36:713-8. [PMID: 21780920 DOI: 10.3109/02713683.2011.584370] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
PURPOSE The aim of this study was to establish the antioxidant status and oxidative stress in patients with primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEG). METHODS Serum levels of total antioxidant capacity (TAC) and superoxide dismutase (SOD) as indicators of antioxidant status; and total oxidant status (TOS), nitric oxide (NO), protein carbonyl (PC), and malondialdehyde (MDA) as indicators of oxidative stress were measured from the blood samples of patients with POAG (n = 23), PEG (n = 24) and healthy control subjects (n = 19) by spectrophotometry. RESULTS Mean TAC level was 0.6 ± 0.1 mmol/L in the POAG group; 0.5 ± 0.1 mmol/L in the PEG group and 1.2 ± 0.3 mmol/L in the control group (p = 0.001). Mean SOD level was 13 ± 0.5 mg/L in the POAG group, 11.6 ± 0.2 mg/L in the PEG group and 9.4 ± 0.6 mg/L in the control group (p = 0.001). Mean TOS level was 19.6 ± 2.6 μmol/L in the POAG group, 21.2 ± 4.2 μmol/L in the PEG group and 15.1 ± 7 μmol/L in the control group (p = 0.001). Mean NO level was 74.3 ± 14.4 µmol/L in the POAG group, 66.1 ± 8.1 µmol/L in the PEG group and 62.3 ± 13.5 µmol/L in the control group (p = 0.005). Mean PC level was 641.5 ± 102.5 nmol/mg in the POAG group, 988.3 ± 214.7 nmol/mg in the PEG group and 654.4 ± 150.7 nmol/mg in the control group (p = 0.001). Mean MDA level was 1.9 ± 0.2 µmol/L in the POAG group, 1.7 ± 0.4 µmol/L in the PEG group and 1.1 ± 0.2 µmol/L in the control group (p = 0.001). CONCLUSION The findings of the present study are potentially of significance and add to the growing body of evidence for oxidative stress in POAG and PEG. Decreased antioxidant defense and increased oxidative stress system may play an important role in the pathogenesis of POAG and PEG.
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Affiliation(s)
- Mesut Erdurmuş
- Department of Ophthalmology, Fatih University Medical School, Ankara, Turkey.
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Karasneh JA, Darwazeh AMG, Hassan AF, Thornhill M. Association between recurrent aphthous stomatitis and inheritance of a single-nucleotide polymorphism of the NOS2 gene encoding inducible nitric oxide synthase. J Oral Pathol Med 2011; 40:715-20. [PMID: 21481004 DOI: 10.1111/j.1600-0714.2011.01039.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Recurrent aphthous stomatitis is a common ulcerative disease of the oral mucosa. Recurrent oral aphthous ulceration is also a feature of the more serious and systemic Behçet's disease. Nitric oxide is a free radical synthesized by one of a family of nitric oxide synthase (NOS) enzymes and is an important regulator of inflammation and immunity. Association of NOS3 gene polymorphisms encoding endothelial nitric oxide synthase has been reported in Behçet's disease but not recurrent aphthous stomatitis. The aim of this study was to investigate any association between NOS2 gene polymorphisms that encode inducible nitric oxide synthase and recurrent aphthous stomatitis. METHODS This is a case control association study. Eighty-three Jordanian recurrent aphthous stomatitis patients and 83 age, gender and ethnically matched controls were genotyped for three NOS2 single-nucleotide polymorphisms, rs10459953, rs1060822 and rs2297518. Chi-squared analysis was used to compare the allele frequencies and genotypes. RESULTS There was a significant association between recurrent aphthous stomatitis and inheritance of single-nucleotide polymorphism rs2297518 (P = 0.006). Although no direct association was demonstrated between rs10459953 or rs1060822 and recurrent aphthous stomatitis, a strong linkage disequilibrium was identified between rs1060822 and rs2297518. CONCLUSION Inheritence of a NOS2 single-nucleotide polymorphism rs2297518 is associated with increased risk of recurrent aphthous stomatitis in a Jordanian population. Confirmatory studies in other populations and investigation of other NOS2 gene polymorphisms will enhance our understanding of the functional basis of this association and help elucidate the role of inducible nitric oxide synthase in recurrent aphthous stomatitis.
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Affiliation(s)
- Jumana A Karasneh
- Department of Oral Medicine and Oral Surgery, Faculty of Dentistry, Jordan University of Science and Technology, Irbid, Jordan.
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Onur E, Kabaroglu C, Inanir I, Var A, Guvenc Y, Gunay O, Gunduz K. Oxidative stress impairs endothelial nitric oxide levels in Behçets' disease. Cutan Ocul Toxicol 2011; 30:217-20. [PMID: 21345164 DOI: 10.3109/15569527.2011.554480] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Behçet's disease (BD) is an inflammatory vasculitis. Endogenous nitric oxide (NO), produced by endothelial cells, has pleiotropic effects such as vasodilatator, antiplatelet, antiproliferative. Reactive oxygen species (ROS) are produced at sites of endothelial inflammation. ROS target polyunsaturated lipids, which results in malondialdehyde (MDA) production. OBJECTIVE The aim was to investigate the oxidative stress in BD patients by measuring MDA and total antioxidant status (TAS) levels and to establish a possible relationship with respect to NO levels regarding disease activity. MATERIALS AND METHODS 55 BD patients (30 active/25 inactive) and 20 healthy volunteers were included in the study. Blood samples were drawn following an overnight fasting. TAS and MDA levels were determined spectrophotometrically. Serum nitrite (NO(2-)) and nitrate (NO(3-)) levels were measured to estimate NO production. Data were expressed as mean ± SD. RESULTS TAS levels were significantly lower in BD patients than the controls (1.19 ± 0.34 vs. 3.29 ± 0.89 mmol/L). In the active BD group, MDA levels (0.36 ± 0.19 nmol/mL) were significantly higher than both the inactive BD group (0.25 ± 0.18 nmol/mL) and controls (0.18 ± 0.41 nmol/mL). NO levels were significantly lower in the active group compared to the inactive group (18.0 ± 2.80 vs. 19.40 ± 2.70 µmol/L). MDA levels correlated negatively with NO levels in the active group. CONCLUSION Decreased NO levels mediated by increased oxidative stress significantly contribute to endothelial dysfunction observed in BD.
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Affiliation(s)
- Ece Onur
- Celal Bayar University School of Medicine, Department of Biochemistry, Manisa, Turkey.
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DNA damage and its relationship with other oxidative stress parameters in Behcet’s disease. Rheumatol Int 2010; 32:217-22. [DOI: 10.1007/s00296-010-1605-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2010] [Accepted: 08/23/2010] [Indexed: 12/13/2022]
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Lee YJ, Kang SW, Baek HJ, Choi HJ, Bae YD, Kang EH, Lee EY, Lee EB, Song YW. Association between matrix metalloproteinase 9 promoter polymorphisms and Behçet's disease. Hum Immunol 2010; 71:717-22. [DOI: 10.1016/j.humimm.2010.03.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2009] [Revised: 03/12/2010] [Accepted: 03/22/2010] [Indexed: 11/27/2022]
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Mahgoub M, Raslan H, Assal H, Gheita T, Fikry I, El-Moniem MA, Anwar M. Oxidant/Antioxidant Status in Patients with Behçet Disease. MACEDONIAN JOURNAL OF MEDICAL SCIENCES 2010; 3:37-42. [DOI: 10.3889/mjms.1857-5773.2010.0087] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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La Regina M, Gasparyan AY, Orlandini F, Prisco D. Behçet's Disease as a Model of Venous Thrombosis. Open Cardiovasc Med J 2010; 4:71-7. [PMID: 20360979 PMCID: PMC2847254 DOI: 10.2174/1874192401004020071] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2009] [Revised: 11/23/2009] [Accepted: 12/12/2009] [Indexed: 01/11/2023] Open
Abstract
Behçet's disease (BD) is a chronic inflammatory disease of unknown aetiology characterized by recurrent oral, genital aphthous ulcerations, uveitis, skin lesions and other multisystem affections associated with vasculitis. Different types of vessels, predominantly veins, can be affected in BD. The frequency of vascular lesions in BD, such as superficial and deep venous thromboses, arterial aneurysms and occlusions, ranges between 7-29%. In this review, various factors of thrombogenesis in BD, particularly pro- and antithrombotic endothelial and non-endothelial factors, factors of coagulation, platelet activation and rheological changes are presented and discussed from positions of Virchow's triad of venous thrombosis. Despite advances in understanding of thrombogenesis in BD, still many issues of diagnosis and targeted preventive and therapeutic measures remain unresolved. Further studies are needed to clarify the pathobiology of BD-related thrombosis and to provide the clinicians with recommendations over the utility, safety and effectiveness of the antithrombotic therapy in BD.
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Affiliation(s)
- Micaela La Regina
- Department of Internal Medicine, Periodic Fevers Research Centre, Catholic University, Rome, Italy
| | | | | | - Domenico Prisco
- Department of Medical and Surgical Critical Care, University of Florence, Florence, Italy
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Regina ML, Gasparyan AY, Orlandini F, Prisco D. Behçet’s Disease as a Model of Venous Thrombosis. Open Cardiovasc Med J 2010. [DOI: 10.2174/1874192401004010071] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Behçet’s disease (BD) is a chronic inflammatory disease of unknown aetiology characterized by recurrent oral, genital aphthous ulcerations, uveitis, skin lesions and other multisystem affections associated with vasculitis. Different types of vessels, predominantly veins, can be affected in BD. The frequency of vascular lesions in BD, such as superficial and deep venous thromboses, arterial aneurysms and occlusions, ranges between 7-29%.
In this review, various factors of thrombogenesis in BD, particularly pro- and antithrombotic endothelial and non-endothelial factors, factors of coagulation, platelet activation and rheological changes are presented and discussed from positions of Virchow’s triad of venous thrombosis.
Despite advances in understanding of thrombogenesis in BD, still many issues of diagnosis and targeted preventive and therapeutic measures remain unresolved. Further studies are needed to clarify the pathobiology of BD-related thrombosis and to provide the clinicians with recommendations over the utility, safety and effectiveness of the antithrombotic therapy in BD.
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Abstract
OBJECTIVE To determine the role of oxidative stress and the antioxidant defense mechanism in the etiopathogenesis of active and inactive Behçets disease. In line with this objective, the present study aimed to examine the levels of nitric oxide (NO) and malondialdehyde (MDA), which are the end products of oxidant stress, and vitamins, which are non-enzymatic antioxidants, for the diagnosis and particularly the follow-up of Behçet's disease. MATERIALS AND METHODS The study group consisted of a total of 60 individuals: 40 of whom were Behçet's disease patients and 20 were healthy individuals. Of the 40 Behçet's patients, 29 had the active and 11 had the inactive (stable) form of the disease. RESULTS Although plasma MDA and NO (its stable form nitrite) levels in the total patient group were statistically significantly higher than those in the control group (p<0.06), there was no statistically significant difference as such between inactive Behçet's patients and the control group (p>0.05). Vitamin E, C, B1, B2 and flavin mononucleotide (FMN) values were significantly lower in the patient group in comparison with the control group (p<0.05). There was no statistically significant difference in other vitamin values. DISCUSSION It is contemplated that measurement of such oxidative stress factors as MDA and NO and an accompanying evaluation of the antioxidant defense system can be significant in the diagnosis and treatment follow-up of Behçet's disease.
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Affiliation(s)
- Basak Kandi
- Departments of Dermatology, Faculty of Medicine, Firat University, Elazig, Turkey.
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Erturan I, Basak PY, Ozturk O, Ceyhan AM, Akkaya VB. Is there any relationship between serum and urine neopterin and serum interferon-gamma levels in the activity of Behcet's disease? J Eur Acad Dermatol Venereol 2009; 23:1414-8. [PMID: 19522774 DOI: 10.1111/j.1468-3083.2009.03334.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Behcet's disease (BD) is a chronic, inflammatory, multisystem vasculitic disorder. There is no reliable laboratory marker that indicates disease activity. Neopterin is an immunological marker of cellular immune activation, which is secreted by monocytes/macrophages as a result of interferon-gamma (IFN-gamma) secretion by activated T lymphocytes. OBJECTIVE We aimed to investigate serum and urine neopterin levels in BD patients. METHODS Forty-five patients who were diagnosed according to the criteria of the International Study Group for BD and 45 age- and sex-matched healthy controls were enrolled in the study. Disease activity was considered by clinical findings. Serum and urine neopterin levels and serum IFN-gamma levels were measured. RESULTS The mean values of serum and urine neopterin levels were 12.68 +/- 4.87 nmol/L and 167.53 +/- 148.73 micromol/mol creatinine, respectively, in BD patients (P = 0.000 and P = 0.008, respectively), which were statistically significantly different from the control group. However, there was no significant statistical difference between serum and urine neopterin levels of the clinically active and inactive patients. It was also found that the mean value of serum IFN-gamma levels was higher in healthy controls than in BD patients (P = 0.000). CONCLUSIONS We conclude that serum and urinary neopterin measurement can not be used as a reliable laboratory marker as the BD patients' serum and urinary neopterin levels do not increase in the active stage even though these levels increase when compared to healthy controls.
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Affiliation(s)
- I Erturan
- Department of Dermatology, School of Medicine, Suleyman Demirel University, Isparta, Turkey.
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Nowatzky J, Chajek-Shaul T. Biomarkers in Behçet’s disease: diagnosis and disease activity. ACTA ACUST UNITED AC 2009. [DOI: 10.2217/ijr.09.22] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Karasneh JA, Baszrafshani R, Thornhill M, Ollier WER. Endothelial nitric oxide synthase gene polymorphisms are not associated with recurrent aphthous stomatitis. Arch Oral Biol 2009; 54:583-7. [PMID: 19410237 DOI: 10.1016/j.archoralbio.2009.03.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2009] [Revised: 02/10/2009] [Accepted: 03/11/2009] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of the oral mucosa. Recurrent oral aphthous ulceration is the most common and consistent feature of the more serious and systemic Behçet's disease (BD). Association of endothelial nitric oxide synthase (eNOS) gene polymorphisms with BD have been reported in different populations. This study aims to investigate if there is an association between these polymorphisms and RAS. METHODS A case-control association study using 91 Caucasoid RAS patients and 91 ethnically matched systemically healthy controls were genotyped for the -786 and 894 eNOS single nucleotide polymorphisms (SNPs) and a variable number of tandem repeat (VNTR) polymorphism. Chi-square analysis was used to compare the allele and genotype frequencies. RESULTS No significant difference was found in the distribution of allele and genotype frequencies of the -786 and +894 polymorphisms or the VNTR polymorphism between cases and controls. CONCLUSION eNOS gene polymorphisms associated with BD are not associated with RAS. This suggests that the oral ulceration common to both conditions may have a different underlying genetic aetiology. Although our data suggests that RAS does not have an association with eNOS, it is still possible that nitric oxide is involved in the disease process. This could still occur through localised and inflammation driven regulation by iNOS.
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Affiliation(s)
- Jumana A Karasneh
- Department of Oral Medicine & Oral Surgery, Dental School, Jordan University of Science & Technology, PO Box 3030, Irbid, Jordan.
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Uveitis associated with pediatric behçet disease in the american midwest. Am J Ophthalmol 2008; 146:819-27.e2. [PMID: 18672222 DOI: 10.1016/j.ajo.2008.05.043] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2008] [Revised: 05/14/2008] [Accepted: 05/26/2008] [Indexed: 11/23/2022]
Abstract
PURPOSE To describe demographics, clinical course, treatment, and visual prognosis of uveitis in pediatric patients with Behçet disease, and to compare childhood-onset with adult-onset Behçet uveitis. DESIGN Retrospective, observational case series. METHODS setting: Uveitis service, University of Illinois at Chicago and private office of one of the authors (H.H.T.). study population: Patients diagnosed with Behçet uveitis using International Study Group criteria between January 1, 1973 to December 31, 2007. main outcome measures: Demographics, symptoms, clinical course, management, laboratory tests, complications, and visual prognoses were recorded. RESULTS Thirty-three patients had available records with at least one month follow-up; four were children and 29 were adults. All children and 19 adults were male. The most common initial symptom was oral ulcers and the most common uveitis type was panuveitis with retinal vasculitis in both groups. There was an average delay of one year among children and 1.8 years among adults between onset of uveitis and disease diagnosis. Immunosuppressive therapy was employed in all children and 23 of 29 adults. Treatment response was variable in both groups. Maculopathy was the most common cause of permanent visual impairment, both in children and in adults. Six of eight pediatric eyes (75%) and 13 of 25 adult eyes (52%) retained a visual acuity better than 20/200 at three years. CONCLUSIONS Behçet disease is an uncommon cause of uveitis in the United States, with a male predominance. Although the clinical picture of Behçet uveitis was similar among both groups, the visual prognosis appeared worse in adults. Awareness of this disease should be increased in nonendemic areas to prevent blindness resulting from delays in diagnosis.
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Ben Dhifallah I, Houman H, Khanfir M, Hamzaoui K. Endothelial nitric oxide synthase gene polymorphism is associated with Behçet's disease in Tunisian population. Hum Immunol 2008; 69:661-5. [PMID: 18718857 DOI: 10.1016/j.humimm.2008.07.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2008] [Revised: 07/15/2008] [Accepted: 07/18/2008] [Indexed: 01/08/2023]
Affiliation(s)
- Imene Ben Dhifallah
- Homeostasis and Cell Dysfunction Unit Research 99/UR/08-40, Medicine University Tunis, Tunisia.
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Cumurcu T, Ozyurt H, Demir HD, Yardim H. Serum alpha-1-antitriypsin levels in patients with pseudoexfolative syndrome. Curr Eye Res 2008; 33:159-62. [PMID: 18293186 DOI: 10.1080/02713680701861752] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE To evaluate the levels of serum alpha 1-antitrypsin in patients with pseudoexfoliation syndrome (PEX) and healthy control subjects without PEX. MATERIAL AND METHODS Forty-four patient with PEX and 40 healthy control subjects (84 subjects total) were enrolled into the study. Serum ATT levels were measured using nephelometry. RESULTS The mean serum AAT concentration in PEX group was significantly higher than in the controls (p=0.0001). CONCLUSION Serum AAT levels were found to be increased in patients with PEX. Increased serum AAT levels in PEX may explain the role of inflammation in this group of patients.
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Affiliation(s)
- Tongabay Cumurcu
- Department of Ophthalmology, Gaziosmanpasa University School of Medicine, Tokat, Turkey.
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Evereklioglu C, Ozbek E, Cekmen M, Mehmet N, Duygulu F, Ozkiris A, Calip M, Er H, Turkoz Y. Urinary nitric oxide levels are increased and correlated with plasma concentrations in patients with Behçet's disease: is it a new urinary activity marker? Nephrology (Carlton) 2008; 8:231-8. [PMID: 15012709 DOI: 10.1046/j.1440-1797.2003.00180.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Nitric oxide (NO) is a free radical and serves many functions within the kidney. Excess NO causes glomerular injury. Behçet's disease (BD) is a systemic immunoinflammatory vasculitis, affecting every organ in the body including the kidneys (subclinic glomerulonephritis). We investigated the role of urinary total nitrite levels (end product of NO) in BD and evaluated whether urinary concentrations were correlated with its plasma levels or disease activity. Thirty-six consecutive Behçet's patients (19 men, 17 women; 35.9 years), and 20 age- and sex-matched healthy control volunteers (12 men, eight women; 33.2 years) were divided into an active (n = 16) and inactive (n = 20) period. Urinary and serum NO levels ( micromol/mg urinary creatinine) were higher in BD patients (4.1 +/- 0.3) than control subjects (1.7 +/- 0.2; P < 0.001). Serum NO levels in Behçet's patients and control subjects were 51.3 +/- 9.8 and 21.7 +/- 7.3 micromol/L, respectively (P < 0.001). Active patients had higher urinary NO excretion (4.9 +/- 0.3) than inactive patients (3.3 +/- 0.3; P < 0.01). Urinary NO levels were correlated with its serum levels (r2 = 0.69, P < 0.001). Higher urinary NO levels found in BD may be produced by the kidney as a result of an inflammatory stimulation. As excess NO is toxic to the tissues, increased NO levels may play a role in mediating subclinic glomerular injury of such patients. However, we could not determine the exact site(s) of NO synthesis by the kidney, such as the glomeruli, blood vessels and/or the tubular cells. Whatever the source, urinary NO levels may be used as a new activity marker in the diagnosis and follow up of BD by serial measurements.
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Affiliation(s)
- Cem Evereklioglu
- Department of Ophthalmology, Erciyes University Medical Faculty, Kayseri, Turkey.
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Taner E, Coşar B, Burhanoğlu S, Calikoğlu E, Onder M, Arikan Z. Depression and anxiety in patients with Behçet's disease compared with that in patients with psoriasis. Int J Dermatol 2007; 46:1118-24. [PMID: 17988328 DOI: 10.1111/j.1365-4632.2007.03247.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Ender Taner
- Department of Psychiatry and Dermatology, Faculty of Medicine, Gazi University, Ankara, Turkey.
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Lee YJ, Kang SW, Song JK, Baek HJ, Choi HJ, Bae YD, Ryu HJ, Lee EY, Lee EB, Song YW. Associations between interferon regulatory factor–1 polymorphisms and Behçet’s disease. Hum Immunol 2007; 68:770-8. [PMID: 17869652 DOI: 10.1016/j.humimm.2007.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2007] [Revised: 05/24/2007] [Accepted: 06/08/2007] [Indexed: 01/29/2023]
Abstract
Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates the functions of type I and II interferons and plays a role in host protection. Behçet's disease (BD) is an idiopathic systemic vasculitis that is often complicated with thrombotic features, and infectious agents have long been postulated to be a disease-triggering factor in its pathogenesis. The authors investigated the distributions of IRF-1 promoter -415 C/A, -410 A/G, and -300 A/G, and 3'-untranslated region (UTR) A/G polymorphisms in 105 BD patients (mean age 41.7 +/- SEM 1.1 years, 44 male and 61 female) and in 105 gender- and age-matched healthy controls. The frequencies of individual alleles and genotypes were not different between the control and BD groups. However, the frequency of AGGG haplotype was significantly higher (73.5% vs 60.2%, odds ratio [OR] = 1.842, 95% confidence interval [95% CI] = 1.219-2.783, p(c) = 0.036) and that of the CAAG haplotype was significantly lower (2.2% vs 9.5%, OR = 0.195, 95% CI = 0.068-0.559, p(c) = 0.02) in BD patients than in healthy controls. In addition, the frequency of the AGGG haplotype was significantly higher (80.3% vs 57.4%, OR = 3.033, 95% CI = 1.716-5.360, p(c) = 0.001) and that of the CAAG haplotype was significantly lower (0.8% vs 12.3%; OR = 0.059, 95% CI = 0.010-0.357, p(c) = 0.005) in female BD patients than female controls. By subgroup analyses, the CAAA haplotype tended to be more common in BD patients with moderate or severe disease than in those with mild disease (25.4% vs 13.6%, OR = 2.158, 95% CI = 1.046-4.440, p = 0.037 before Bonferroni correction). When BD patients were subclassified by a history of deep vein thrombosis (DVT), the CAAA haplotype was found to be significantly increased the risk of DVT (42.1% vs 15.7%, OR = 3.906, 95% CI = 1.836-8.324, p(c) = 0.0015) and the AGGG haplotype tended to reduce this risk (57.9% vs 77.3%, OR = 0.403, 95% CI = 0.195-0.834, p(c) = 0.0685). Furthermore, the frequency of the CAAA haplotype was significantly higher in BD patients that had experienced a thrombotic event than in those that had not (40.5% vs 15.5%, OR = 3.7147, 95% CI = 1.778-7.770, p(c) = 0.0015). These results suggest that IRF-1 is a novel susceptibility gene in BD, especially in women, and furthermore, that IRF-1 polymorphisms may be related to thrombosis in BD patients.
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Affiliation(s)
- Yun Jong Lee
- Department of Internal Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
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Guenane H, Hartani D, Chachoua L, Lahlou-Boukoffa OS, Mazari F, Touil-Boukoffa C. [Production of Th1/Th2 cytokines and nitric oxide in Behçet's uveitis and idiopathic uveitis]. J Fr Ophtalmol 2007; 29:146-52. [PMID: 16523155 DOI: 10.1016/s0181-5512(06)73762-7] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
INTRODUCTION The aim of this study was to investigate the role of Th1 (IFN-gamma and IL-12), Th2 (IL-10) cytokines and nitric oxide (NO) in the immunopathologic mechanisms of uveitis related to Behçet's disease and isolated idiopathic uveitis. PATIENTS AND METHOD This study was conducted on 24 patients with Behçet's syndrome who had active uveitis, ten of whom showed isolated uveitis classified as idiopathic uveitis, and 13 healthy controls. The levels of IFN-gamma, IL-12 and IL-10 in sera and supernatants of PBMC cultures stimulated by PHA were estimated using immunoenzymatic dosage (ELISA sandwich according to the methods recommended by Immunotech France). The production of NO was measured in vivo and in vitro for the same patients using the modified Griess method. RESULTS The induction of IFN-gamma and IL-12 was higher in the two groups of patients than in the controls (P<0.001). Significant IL-10 levels were recorded in 56.5% of patients with Behçet's disease presenting uveitis versus 30% of patients with idiopathic uveitis. NO production was more pronounced in idiopathic uveitis than in Behçet's syndrome (P<0.02). CONCLUSION The predominance of the Th1 profile was associated with high production of NO in idiopathic uveitis. A Th1/Th2 profile with a moderated increase in NO production was observed in Behçet's disease. Our data have a clinical impact. The observation of combined Th1/Th2 cytokines and NO elevation in both in vivo an in vitro experiments could have a predictive value in characterizing uveitis associated with Behçet's disease.
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Affiliation(s)
- H Guenane
- Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, USTHB Bab Ezzouar, Alger, Algérie.
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Evereklioglu C. The treatment schedule and historical naming process of Behçet disease. J Eur Acad Dermatol Venereol 2007; 21:427-8. [PMID: 17309491 DOI: 10.1111/j.1468-3083.2006.01921.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Amoura Z, Guillaume M, Caillat-Zucman S, Wechsler B, Piette JC. Physiopathologie de la maladie de Behçet. Rev Med Interne 2006; 27:843-53. [PMID: 16828934 DOI: 10.1016/j.revmed.2006.02.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2006] [Accepted: 02/22/2006] [Indexed: 12/27/2022]
Abstract
SUBJECT Pathophysiology of Behçet's disease (BD) is complex. Recent experimental data shed new light on the mechanisms leading to organ lesions. MAIN ISSUES Neutrophils and cytotoxic lymphocytes are now recognized as key effector cells in BD. Genetic susceptibility, environmental factors (virus and/or bacterial infections), inflammatory response abnormalities (heat shock proteins, dysregulated NO production) and abnormal immune response play also a major role in BD pathogeny. PERSPECTIVES Better understanding of the BD pathophysiology will allow the development of new therapies more specific of BD.
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Affiliation(s)
- Z Amoura
- Centre national de référence maladies rares, service de médecine interne, hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75013 Paris, France.
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Lee YJ, Kang SW, Park JJ, Bae YD, Lee EY, Lee EB, Song YW. Interleukin-18 Promoter Polymorphisms in Patients With Behçet’s Disease. Hum Immunol 2006; 67:812-8. [PMID: 17055358 DOI: 10.1016/j.humimm.2006.07.012] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2006] [Revised: 07/11/2006] [Accepted: 07/21/2006] [Indexed: 11/23/2022]
Abstract
Behçet's disease (BD) is an idiopathic systemic inflammatory disease and is considered to be a T helper 1 (Th1) type cytokine driven disorder. Moreover, levels of interleukin-18 (IL-18), a pivotal mediator of Th1 cytokine response, have been reported to be upregulated in BD. Therefore, we investigated the distribution of IL-18 promoter -607 C/A and -137 G/C polymorphisms in 103 BD patients (mean age 41.0 years; 48 male, 55 female) using allele-specific-polymerase chain reaction. As compared with healthy control subjects, BD patients had a significantly higher frequency of the -607 CC genotype (42.7% vs 23.3%, odds ratio [OR] = 2.455, 95% confidence interval [CI] = 1.350-4.461, p(c) = 0.021) and a higher frequency of the -607 C allele (60.7% vs 48.1%, OR = 1.668, 95% CI = 1.129-2.464, p = 0.0101). Haplotype analysis showed that BD patients had significantly less -607A/-137G haplotype (27.3% vs 44.2%, OR = 0.469, 95% CI = 0.268-0.820, p(c) = 0.032) and -607A/-137G haplotype homozygote (5.8% vs 20.4%, OR = 0.242, 95% CI = 0.096-0.612, p(c) = 0.014) than control subjects. In addition, the frequency of -607C/-137G haplotype homozygote was significantly higher in BD patients than control subjects (48.5% vs 20.4%, OR = 3.684, 95% CI = 1.997-6.791, p(c) = 0.0014). Although there were no associations between the polymorphisms and clinical manifestations or severity, patients with the -607 CC genotype or -607C/-137G haplotype homozygote showed significantly earlier symptom development (p = 0.034 by ANOVA; p = 0.009 by t-test, respectively) than those with other genotypes or diplotypes. These results suggest that the IL-18 promoter gene is a candidate susceptibility gene in BD patients.
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Affiliation(s)
- Yun Jong Lee
- Department of Internal Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea
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Shaker O, Ay El-Deen MA, El Hadidi H, Grace BD, El Sherif H, Abdel Halim A. The role of heat shock protein 60, vascular endothelial growth factor and antiphospholipid antibodies in Behçet disease. Br J Dermatol 2006; 156:32-7. [PMID: 17199563 DOI: 10.1111/j.1365-2133.2006.07536.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Behçet disease is a systemic inflammatory disease of unknown aetiology. T cells in this disease proliferate vigorously in response to a specific peptide of heat shock protein (HSP) 60 in an antigen-specific fashion. Vascular endothelial cell growth factor (VEGF) is a cytokine participating in the inflammatory process. One of the prominent features of Behçet disease is vasculitis as a result of endothelial dysfunction. Antiphospholipid antibodies (APA) may play a role in the development of thrombosis by inhibiting production of prostacyclin by endothelial cells. OBJECTIVES To investigate the role of HSP60, VEGF and APA in Behçet disease and their relation to clinical manifestations and disease activity. METHODS Thirty patients with Behçet disease were included; 17 were in the active stage and 13 were in the inactive. Fifteen age- and sex-matched healthy subjects served as controls. Complete clinical examination and Doppler examination were done. Serum levels of HSP60, VEGF and APA were performed. RESULTS Serum levels of HSP60, VEGF and APA were significantly higher in patients than in controls; however, their level did not correlate with disease activity. The serum level of VEGF correlated significantly with the presence of vascular manifestations and ocular involvement. The serum level of APA was greater in patients with thrombosis. HSP60 has an important role in aetiopathogenesis of Behçet disease, which sheds new light on its autoimmune nature. CONCLUSIONS An elevated serum level of VEGF may be a risk factor for the development of ocular disease contributing to poor visual outcome.
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Affiliation(s)
- O Shaker
- Department of Medical Biochemistry, Faculty of Medicine, Kasr El Aini Hospital, Cairo University, Cairo, Egypt.
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Evereklioglu C. Diagnostic dilemma between intestinal Behçet disease and inflammatory bowel disease with pyoderma gangrenosum. World J Gastroenterol 2006; 12:5748-51. [PMID: 17007037 PMCID: PMC4088185 DOI: 10.3748/wjg.v12.i35.5748] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Evereklioglu C. Regarding neutrophil and lymphocyte responses to oralStreptococcusin AdamantiadesâBehçet's disease. ACTA ACUST UNITED AC 2006; 47:311-4. [PMID: 16872367 DOI: 10.1111/j.1574-695x.2006.00135.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Aliyazicioglu Y, Ozkaya O, Yakut H, Islek I, Alvur M. Leptin levels in Henoch–Schönlein purpura. Clin Rheumatol 2006; 26:371-5. [PMID: 16816886 DOI: 10.1007/s10067-006-0363-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2005] [Revised: 09/05/2005] [Accepted: 09/09/2005] [Indexed: 10/24/2022]
Abstract
The objective of this paper is to assess the possible role of nitric oxide (NO) and leptin in Henoch-Schönlein purpura (HSP). We investigated the serum leptin and total nitrite levels in 22 children with HSP in the acute phase and after remission and in 20 age- and sex-matched healthy control. Serum leptin levels (nanograms per milliliter; median, min-max) were statistically higher in the acute phase (12.9, 9.1-19.5) than those in the remission phase (6.1, 3.7-10.5, p<0.001) and in the control group (4.9, 3.8-7.5, p<0.001). Also, serum nitrite levels (micromole per liter; median, min-max) were higher in children in the acute phase (45.0, 32.0-60.0) compared to those in remission phase (30.5, 23.0-48.0) and in the control group (29.5, 18.0-38.0) (p<0.001, p<0.001, respectively). There was a positive correlation between serum leptin and total nitrite levels (r=0.65, p<0.001). We have demonstrated that serum leptin and NO levels were increased during the acute phase in children with HSP, and returned to normal levels in remission. We suggest that leptin and NO may have a role in the immunoinflammatory process of HSP, especially in the acute phase. Further studies are needed to clearly establish the roles of leptin and NO in the pathogenesis of HSP.
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Affiliation(s)
- Yuksel Aliyazicioglu
- Department of Biochemistry, Faculty of Medicine, Ondokuz Mayis University, 55139, Samsun, Turkey.
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