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Kuballa A, Geraci M, Johnston M, Sorrentino D. The Gut Microbial Profile of Preclinical Crohn's Disease Is Similar to That of Healthy Controls. Inflamm Bowel Dis 2020; 26:1682-1690. [PMID: 32339246 DOI: 10.1093/ibd/izaa072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS It is unclear whether microbial dysbiosis plays an etiologic role in Crohn's disease (CD) or is the result of protracted inflammation. Here, we test the hypothesis that dysbiosis predates clinical CD in asymptomatic first-degree relatives (FDRs) of CD patients: normal (FDR1), with borderline inflammation (FDR2), and with frank, very early inflammation (FDR3). METHODS The gut microbial diversity was tested in ileocecal biopsies through next generation sequencing of the 16S rRNA gene in 10 healthy controls (HCs), 22 patients with active, untreated CD, and 25 FDRs (9 FDR1; 12 FDR2; 4 FDR3). The metagenomic functions of 41 microbiome-related processes were inferred by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis. RESULTS Compared with HCs, alpha diversity in CD patients was decreased, with an observed decrease in Faecalibacterium prausnitzii and increase in Bacteroides fragilis. In FDRs, microbial diversity was unchanged compared with HCs. In Operational Taxonomic Units and PICRUSt Principal coordinates and component analyses, the ellipse centroid of FDRs was diagonally opposed to that of CD patients, but close to the HC centroid. In both analyses, statistically significant differences in terms of beta diversity were found between CD and HC but not between FDR and HC. CONCLUSIONS In FDRs (including FDR3-who bear preclinical/biologic onset disease), we found that the microbial profile is remarkably similar to HC. If confirmed in larger studies, this finding suggests that clinical CD-associated dysbiosis could result from the changed microenvironment due to disease evolution over time.
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Affiliation(s)
- Anna Kuballa
- Inflammation Research Cluster, School of Health and Sport Sciences, University of the Sunshine Coast, Sippy Downs, QLD, Australia
| | - Marco Geraci
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Meredith Johnston
- Inflammation Research Cluster, School of Health and Sport Sciences, University of the Sunshine Coast, Sippy Downs, QLD, Australia
| | - Dario Sorrentino
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA.,Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, Udine, Italy
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Chakaroun RM, Massier L, Kovacs P. Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders? Nutrients 2020; 12:E1082. [PMID: 32295104 PMCID: PMC7230435 DOI: 10.3390/nu12041082] [Citation(s) in RCA: 177] [Impact Index Per Article: 35.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 04/07/2020] [Indexed: 02/06/2023] Open
Abstract
The emerging evidence on the interconnectedness between the gut microbiome and host metabolism has led to a paradigm shift in the study of metabolic diseases such as obesity and type 2 diabetes with implications on both underlying pathophysiology and potential treatment. Mounting preclinical and clinical evidence of gut microbiota shifts, increased intestinal permeability in metabolic disease, and the critical positioning of the intestinal barrier at the interface between environment and internal milieu have led to the rekindling of the "leaky gut" concept. Although increased circulation of surrogate markers and directly measurable intestinal permeability have been linked to increased systemic inflammation in metabolic disease, mechanistic models behind this phenomenon are underdeveloped. Given repeated observations of microorganisms in several tissues with congruent phylogenetic findings, we review current evidence on these unanticipated niches, focusing specifically on the interaction between gut permeability and intestinal as well as extra-intestinal bacteria and their joint contributions to systemic inflammation and metabolism. We further address limitations of current studies and suggest strategies drawing on standard techniques for permeability measurement, recent advancements in microbial culture independent techniques and computational methodologies to robustly develop these concepts, which may be of considerable value for the development of prevention and treatment strategies.
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Affiliation(s)
- Rima M. Chakaroun
- Medical Department III—Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, 04103 Leipzig, Germany; (L.M.); (P.K.)
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Łoniewska B, Adamek K, Węgrzyn D, Kaczmarczyk M, Skonieczna-Żydecka K, Clark J, Adler G, Tousty J, Uzar I, Tousty P, Łoniewski I. Analysis of Faecal Zonulin and Calprotectin Concentrations in Healthy Children During the First Two Years of Life. An Observational Prospective Cohort Study. J Clin Med 2020; 9:jcm9030777. [PMID: 32178435 PMCID: PMC7141325 DOI: 10.3390/jcm9030777] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 03/08/2020] [Accepted: 03/10/2020] [Indexed: 12/16/2022] Open
Abstract
Factors affecting the intestinal-barrier permeability of newborns, such as body mass index (BMI), nutrition and antibiotics, are assumed to affect intestinal-barrier permeability in the first two years of life. This study assessed 100 healthy, full-term newborns to 24 months old. Faecal zonulin/calprotectin concentrations were measured at 1, 6, 12, 24 months as gut-permeability markers. Zonulin concentrations increased between 1 and 12 months (medians: 114.41, 223.7 ng/mL; respectively), whereas calprotectin concentrations decreased between one and six months (medians: 149. 29, 109.28 µg/mL); both then stabilized (24 months: 256.9 ng/mL zonulin; 59.5 µg/mL calprotectin). In individual children, high levels at one month gave high levels at older ages (correlations: calprotectin: between 1 and 6 or 12 months: correlation coefficient (R) = 0.33, statistical significance (p) = 0.0095; R = 0.28, p = 0.032; zonulin: between 1 and 24 months: R = 0.32; p = 0.022, respectively). Parameters which gave marker increases: antibiotics during pregnancy (calprotectin; six months: by 80%, p = 0.038; 12 months: by 48%, p = 0.028); vaginal birth (calprotectin: 6 months: by 140%, p = 0.005); and > 5.7 pregnancy-BMI increase (zonulin: 12 months: by 74%, p = 0.049). Conclusions: “Closure of the intestines” is spread over time and begins between the sixth and twelfth month of life. Antibiotic therapy, BMI increase > 5.7 during pregnancy and vaginal birth are associated with increased intestinal permeability during the first two years of life. Stool zonulin and calprotectin concentrations were much higher compared with previous measurements at older ages; clinical interpretation and validation are needed (no health associations found).
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Affiliation(s)
- Beata Łoniewska
- Department of Neonatal Diseases, Pomeranian Medical University, Szczecin 70-111, Poland; (K.A.); (D.W.); (J.T.)
- Correspondence: ; Tel.: +48-(91)-466-1375
| | - Karolina Adamek
- Department of Neonatal Diseases, Pomeranian Medical University, Szczecin 70-111, Poland; (K.A.); (D.W.); (J.T.)
| | - Dagmara Węgrzyn
- Department of Neonatal Diseases, Pomeranian Medical University, Szczecin 70-111, Poland; (K.A.); (D.W.); (J.T.)
| | - Mariusz Kaczmarczyk
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin 70-111, Poland; (M.K.); (J.C.)
| | - Karolina Skonieczna-Żydecka
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, Szczecin 71-460, Poland; (K.S.-Ż.); (I.Ł.)
| | - Jeremy Clark
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University, Szczecin 70-111, Poland; (M.K.); (J.C.)
| | - Grażyna Adler
- Department of Studies in Anthropogenetics and Biogerontology, Pomeranian Medical University, Szczecin 71-210, Poland;
| | - Joanna Tousty
- Department of Neonatal Diseases, Pomeranian Medical University, Szczecin 70-111, Poland; (K.A.); (D.W.); (J.T.)
| | - Izabela Uzar
- Department of General Pharmacology and Pharmacoeconomics, Pomeranian Medical University, Szczecin 71-230, Poland;
| | - Piotr Tousty
- Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin 70-111, Poland;
| | - Igor Łoniewski
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, Szczecin 71-460, Poland; (K.S.-Ż.); (I.Ł.)
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Sorrentino D, Nguyen VQ, Chitnavis MV. Capturing the Biologic Onset of Inflammatory Bowel Diseases: Impact on Translational and Clinical Science. Cells 2019; 8:E548. [PMID: 31174359 PMCID: PMC6627618 DOI: 10.3390/cells8060548] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2019] [Revised: 05/30/2019] [Accepted: 06/04/2019] [Indexed: 12/16/2022] Open
Abstract
While much progress has been made in the last two decades in the treatment and the management of inflammatory bowel diseases (IBD)-both ulcerative colitis (UC) and Crohn's Disease (CD)-as of today these conditions are still diagnosed only after they have become symptomatic. This is a major drawback since by then the inflammatory process has often already caused considerable damage and the disease might have become partially or totally unresponsive to medical therapy. Late diagnosis in IBD is due to the lack of accurate, non-invasive indicators that would allow disease identification during the pre-clinical stage-as it is often done in many other medical conditions. Here, we will discuss what is known about the biologic onset and pre-clinical CD with an emphasis on studies conducted in patients' first degree relatives. We will then review the possible strategies to diagnose IBD very early in time including screening, available disease markers and imaging, and the possible clinical implications of treating these conditions at or close to their biologic onset. Later, we will review the potential impact of conducting translational research in IBD during the pre-clinical stage, especially focusing on the role of the microbiome in disease etiology and pathogenesis. Finally, we will highlight possible future developments in the field and how they can impact IBD management and our scientific knowledge of these conditions.
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Affiliation(s)
- Dario Sorrentino
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, FRACP 3 Riverside Circle, Roanoke, VA 24016, USA.
- Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, 33100 Udine, Italy.
| | - Vu Q Nguyen
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, FRACP 3 Riverside Circle, Roanoke, VA 24016, USA.
| | - Maithili V Chitnavis
- IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, FRACP 3 Riverside Circle, Roanoke, VA 24016, USA.
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Diagnostic Value of Fecal Calprotectin (S100 A8/A9) Test in Children with Chronic Abdominal Pain. Gastroenterol Res Pract 2016; 2016:8089217. [PMID: 27974886 PMCID: PMC5126428 DOI: 10.1155/2016/8089217] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Revised: 09/28/2016] [Accepted: 10/19/2016] [Indexed: 12/22/2022] Open
Abstract
Objectives. The aim of the study was to establish whether fecal calprotectin concentration (FCC) may be useful in children with chronic abdominal pain to differentiate between inflammatory bowel disease (IBD), other inflammatory gastrointestinal disorders, and functional gastrointestinal disorders. Methods. The study included 163 patients (median age 13 years), who were assigned to four study groups: group 0 (control), 22 healthy children; group 1, 33 children with functional gastrointestinal disorders; group 2, 71 children with inflammatory gastrointestinal disorders other than IBD; group 3, 37 children with IBD. FCC was measured using ELISA assay. Results. In group 0 and group 1 FCCs were below 100 μg/g. Low FCCs were found in 91% of patients in group 2. In patients with IBD FCCs were markedly elevated with median value of 1191.5 μg/g. However, in children with inflammatory gastrointestinal disorders other than IBD and in children with IBD mean FCCs were significantly higher compared with the control group. Significant differences in FCCs were also found between group 1 and group 2, between group 1 and group 3, and between group 2 and group 3. Conclusion. FCC is the best parameter allowing for differentiation between IBD, other inflammatory gastrointestinal disorders, and functional gastrointestinal disorders. High FCC is associated with a high probability of IBD and/or other inflammatory gastrointestinal disorders, and it allows excluding functional gastrointestinal disorders.
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Abstract
Little is known on the natural history of Crohn's disease (CD) before diagnosis. By the time the patient is diagnosed, the disease has often produced considerable damage to the intestinal mucosa and sometimes other organs. Such period before diagnosis might involve both a silent and a symptomatic phase. The silent phase, or preclinical CD, might last several years after the biological disease onset. Evidence is accumulating that the symptomatic phase might also go undiagnosed for months or years. In fact, for each established case of CD, there are probably several undiagnosed cases, a classic iceberg phenomenon of disease. Such status quo--lagging behind diagnostic standards for many other diseases--effectively hampers efforts to block disease evolution and the development of complications. This is no longer tenable because CD is a debilitating, severe, and costly affection, whose incidence is rapidly rising worldwide. Here, we will review what is currently known on preclinical and undiagnosed CD and what could be done to improve accuracy and timeliness of diagnosis.
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Li F, Ma J, Geng S, Wang J, Liu J, Zhang J, Sheng X. Fecal calprotectin concentrations in healthy children aged 1-18 months. PLoS One 2015; 10:e0119574. [PMID: 25742018 PMCID: PMC4351193 DOI: 10.1371/journal.pone.0119574] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Accepted: 01/15/2015] [Indexed: 12/13/2022] Open
Abstract
Objective Fecal calprotectin (FC) is an established biomarker of gut inflammation. The aim of this study was to evaluate FC concentrations in healthy children between 1 and 18 months of age. Methods Healthy children aged 1-18 months were enrolled in this study at the Department of Children's Health Care in Shanghai, China. Children’s stool samples were collected and analyzed, and FC concentration was determined using a commercially available enzyme-linked immunosorbent assay (ELISA). The children's weights and lengths were measured. Parents were asked to complete a brief questionnaire regarding several clinical and sociodemographic factors. Results The FC concentrations were unevenly distributed; the median FC concentration was 174.3 μg/g (range: 6.0-1097.7 μg/g) or 2.241 log10 μg/g (range: 0.775-3.041 log10 μg/g) for all 288 children. The children were divided into several age groups: 1-3 months, 3-6 months, 6-9 months, 9-12 months and 12-18 months. The median FC concentrations for these age groups were 375.2 μg/g (2.574 log10 μg/g), 217.9 μg/g (2.338 log10 μg/g), 127.7 μg/g (2.106 log10 μg/g), 96.1 μg/g (1.983 log10 μg/g) and 104.2 μg/g (2.016 log10 μg/g), respectively. A significant correlation between age and FC concentration was found (r=-0.490, p<0.001). A simple correlation analysis of weight-for-length Z-scores or weight-for-age Z-scores vs. FC concentrations showed that these variables were negatively correlated (Spearman’s rho=-0.287, p<0.001; Spearman’s rho=-0.243, p<0.001, respectively). Conclusions The FC levels of children aged 1-18 months exhibit a downward trend with increasing age and are greater than the normal levels observed in healthy adults. In healthy children aged <6 months, FC levels are high. In children aged 6-18 months, FC concentrations are relatively low but are still higher than those of children aged >4 years.
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Affiliation(s)
- Feng Li
- Department of Children and Adolescents Health Care, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingqiu Ma
- Department of Children and Adolescents Health Care, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shanshan Geng
- Department of Children and Adolescents Health Care, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junli Wang
- Department of Children and Adolescents Health Care, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinrong Liu
- Department of Children and Adolescents Health Care, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Zhang
- Department of Children and Adolescents Health Care, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyang Sheng
- Department of Children and Adolescents Health Care, MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- * E-mail:
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Abstract
BACKGROUND First-degree relatives of patients with Crohn's disease (CD) are at risk of developing the disease with 5% to 15% reported to be affected over time. Yet, a much greater proportion of them (>40%) shows features of "subclinical inflammation" with elevated intestinal inflammatory markers such as fecal calprotectin. The meaning of these findings is unclear in the absence of tissue data. METHODS Thirty-eight asymptomatic first-degree relatives of patients with CD underwent ileocolonoscopy and other tests including fecal calprotectin. All known causes of intestinal inflammation were carefully excluded. Age and gender-matched controls consisted of 10 individuals who underwent colonoscopy for other reasons. Histology was scored based on known methods. RESULTS Compared with controls, the relatives had significantly greater median values for fecal calprotectin and histological scores. In relatives, endoscopy identified 3 different phenotypes: (1) normal, (2) with minor lesions (aphthae or small superficial erosions), and (3) with typical CD inflammation. Based on the histological scores, the clustering analysis produced 3 corresponding highly separated clusters (61%, 26%, and 13% of the total, respectively) with divisive coefficient D = 0.94. When followed up (on the average for 53 mo), individuals in the second cluster had histological scores similar to baseline values (P = 0.12). CONCLUSIONS Tissue studies in first-degree relatives of patients with CD reveal 3 distinct groups: normal, with minimal inflammation, and with frank disease. The second cluster represents a novel phenotype, which does not seem to develop the disease over time. These findings explain previous observations of "subclinical inflammation" in such population.
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Chiu KH, Lee WLW, Chang CC, Chen SC, Chang YC, Ho MN, Hsu JF, Liao PC. A label-free differential proteomic analysis of mouse bronchoalveolar lavage fluid exposed to ultrafine carbon black. Anal Chim Acta 2010; 673:160-6. [PMID: 20599030 DOI: 10.1016/j.aca.2010.05.041] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2010] [Revised: 05/23/2010] [Accepted: 05/30/2010] [Indexed: 10/19/2022]
Abstract
Ultrafine carbon black (ufCB) is a potential hazard to the lung. It causes changes in protein expression and it increases alveolar-capillary permeability in the lung. Label-free quantitative proteomic methods allow a sensitive and accurate analytical method for identifying and quantifying proteins in a protein mixture without chemically modifying the proteins. We used a label-free quantitative proteomic approach that combined and aligned LC-MS and LC-MS/MS spectra to analyze mouse bronchoalveolar lavage fluid (BALF) protein changes associated with exposure to ufCB. We developed a simple normalization method for quantification without spiking the internal standard. The intensities of unchanged peptides were used as normalization factors based on a statistical method to avoid the influence of peptides changed because of ufCB. LC-MS/MS spectra and then database searching were used to identify proteins. The relative abundances of the aligned peptides of identified proteins were determined using LC-MS spectra. We identified 132 proteins, of which 77 are reported for the first time. In addition, the expression of 15 inflammatory proteins and surfactant-associated proteins was regulated (i.e., 7 upregulated and 8 downregulated) compared with the controls. Several proteins not previously reported provide complementary information on the proteins present in mouse BALF, and they are potential biomarkers for the understanding of mechanisms involved in ufCB-induced lung disorders hypothesize that using the label-free quantitative proteomic approach introduced here is well suited for more rigorous, large-scale quantitative analysis of biological samples. We hypothesize that this label-free quantitative proteomic approach will be suited for a large-scale quantitative analysis of biological samples.
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Affiliation(s)
- Kuo-Hsun Chiu
- Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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Montalto M, Curigliano V, Santoro L, Armuzzi A, Cammarota G, Covino M, Mentella MC, Ancarani F, Manna R, Gasbarrini A, Gasbarrini G. Fecal calprotectin in first-degree relatives of patients with ulcerative colitis. Am J Gastroenterol 2007; 102:132-6. [PMID: 17100982 DOI: 10.1111/j.1572-0241.2006.00884.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The pathogenesis of inflammatory bowel disease seems to depend on the combination of genetic and environmental factors. To evaluate genetic susceptibility, one approach is to search for specific markers in apparently unaffected family members of patients. Our aim was to evaluate fecal calprotectin concentrations (FCCs) in first-degree relatives of patients with ulcerative colitis (UC). PATIENTS Fifty-five patients with UC and 167 healthy first-degree relatives were recruited; 38 of the patients' spouses were also enrolled. One hundred fifty healthy subjects participated as the control group. METHODS FCCs were determined by ELISA. FCCs were compared among the groups by Kruskal-Wallis analysis of variance (ANOVA) test followed by Mann-Whitney U test. RESULTS Significantly greater FCCs were found in first-degree relatives of patients with UC (76.0 [34.7-129.6] microg/g) as compared with controls (31.6 [17.0-45.0]) (P < 0.0001). Fecal calprotectin levels in patients with UC (256.0 [153.0-356.0] microg/g) were significantly higher as compared with first-degree relatives, spouses (43.8 [18.6-89.0] microg/g), and controls (P < 0.0001 for all comparisons). FCC of relatives was significantly higher than FCC of spouses (P = 0.01). FCC of spouses had a significantly higher FCC with respect to controls (P = 0.01). CONCLUSIONS First-degree relatives of patients with UC had greater FCC values and could have a subclinical intestinal inflammation. It needs to be clarified if this finding is the consequence of genetic predisposition, of environmental factors, or the interaction of both, and if relatives with high FCC have a greater risk of developing the disease.
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Affiliation(s)
- Massimo Montalto
- Institute of Internal Medicine, Catholic University, Rome, Italy
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Kaner D, Bernimoulin JP, Kleber BM, Heizmann WR, Friedmann A. Gingival crevicular fluid levels of calprotectin and myeloperoxidase during therapy for generalized aggressive periodontitis. J Periodontal Res 2006; 41:132-9. [PMID: 16499716 DOI: 10.1111/j.1600-0765.2005.00849.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Levels of the inflammation marker calprotectin in gingival crevicular fluid correspond to clinical and biochemical parameters of periodontal inflammation. Neutrophil granulocytes (polymorphonuclear neutrophils: PMNs) are supposed to be the main source of calprotectin in gingival crevicular fluid, but evidence is still lacking. The influence of periodontal therapy on gingival crevicular fluid levels of calprotectin has not yet been determined. OBJECTIVES Gingival crevicular fluid levels of calprotectin were monitored during therapy for generalized aggressive periodontitis. Interrelations between calprotectin and the PMN marker myeloperoxidase (MPO) were evaluated. MATERIAL AND METHODS Gingival crevicular fluid samples were collected from 23 patients with generalized aggressive periodontitis before and 3 months after non-surgical therapy with an adjunctive antimicrobial medication. Clinical parameters were recorded with a pressure-calibrated electronic probe. Levels of calprotectin and MPO in gingival crevicular fluid were analysed by enzyme-linked immunosorbent assay (ELISA) procedures. RESULTS At baseline, levels of calprotectin and MPO were highly correlated. Bleeding and suppurating sites showed significantly higher levels of calprotectin and MPO than non-bleeding, non-suppurating sites. Therapy significantly decreased levels of both biomarkers. These changes of calprotectin and MPO were highly correlated and also related to probing-depth reduction. Three months after therapy, the levels of both markers still showed significant correlations in initially deep sites, whereas in initially shallow sites no significant correlation was found. After therapy, levels of markers in bleeding and non-bleeding sites were comparable. CONCLUSION The correlations between calprotectin and MPO indicate that PMNs are a major contributor to the calprotectin content in gingival crevicular fluid of severely affected sites. Calprotectin levels in gingival crevicular fluid and their changes reflect periodontal inflammation as well as the clinical treatment outcome. A prognostic potential of this marker substance remains to be determined.
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Affiliation(s)
- Doğan Kaner
- Department of Periodontology and Synoptic Dentistry, Charité- Universitätsmedizin Berlin, Germany.
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Merkel D, Rist W, Seither P, Weith A, Lenter MC. Proteomic study of human bronchoalveolar lavage fluids from smokers with chronic obstructive pulmonary disease by combining surface-enhanced laser desorption/ionization-mass spectrometry profiling with mass spectrometric protein identification. Proteomics 2005; 5:2972-80. [PMID: 16075419 DOI: 10.1002/pmic.200401180] [Citation(s) in RCA: 104] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Bronchoalveolar lavage fluid (BALF) is an important diagnostic source to investigate cellular and molecular changes in the course of lung disorders. The pattern of soluble proteins in BALF obtained from patients at different stages of respiratory disorders may provide deeper insights in the molecular mechanisms of the disease. We used surface-enhanced laser desorption/ionization mass spectrometry (MS) for differential protein display combined with reversed-phase chromatography and subsequent matrix-assisted laser desorption/ionization-MS or nanoliquid chromatography MS/MS analysis for protein identification to compare the protein pattern of BALF samples obtained from ten smokers suffering from chronic obstructive pulmonary disease (COPD), eight clinically asymptomatic smokers, and eight nonsmokers without pulmonary disease. In this context, we were able to identify small proteins and peptides, either differentially expressed or secreted in the course of COPD or in a direct response to cigarette smoke. The concentrations of neutrophil defensins 1 and 2, S100A8 (calgranulin A), and S100A9 (calgranulin B) were elevated in BALFs of smokers with COPD when compared to asymptomatic smokers. Increased concentrations in S100A8 (Calgranulin A), salivary proline-rich peptide P-C, and lysozyme C were detected in BALFs of asymptomatic smokers when compared to nonsmokers, whereas salivary proline-rich peptide P-D and Clara cell phospholipid-binding protein (CC10) were reduced in their concentration. The identified proteins and peptides might be useful in the future as diagnostic markers for smoke-induced lung irritations and COPD.
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Affiliation(s)
- Dietrich Merkel
- Department of Pulmonary Research, Genomics Group, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany
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