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Yung S, Chan TM. Endothelial cell activation and glycocalyx shedding - potential as biomarkers in patients with lupus nephritis. Front Immunol 2023; 14:1251876. [PMID: 37854589 PMCID: PMC10579905 DOI: 10.3389/fimmu.2023.1251876] [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: 07/02/2023] [Accepted: 09/18/2023] [Indexed: 10/20/2023] Open
Abstract
Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus and an important cause of acute and chronic kidney injury. Early diagnosis of LN and preventing relapses are key to preserving renal reserve. However, due to the complexity and heterogeneity of the disease, clinical management remains challenging. Kidney biopsy remains the gold standard for confirming the diagnosis of LN and subsequent assessment of kidney histopathology, but it is invasive and cannot be repeated frequently. Current clinical indicators of kidney function such as proteinuria and serum creatinine level are non-specific and do not accurately reflect histopathological changes, while anti-dsDNA antibody and C3 levels reflect immunological status but not kidney injury. Identification of novel and specific biomarkers for LN is prerequisite to improve management. Renal function deterioration is associated with changes in the endothelial glycocalyx, a delicate gel-like layer located at the interface between the endothelium and bloodstream. Inflammation induces endothelial cell activation and shedding of glycocalyx constituents into the circulation. This review discusses the potential role of soluble glycocalyx components as biomarkers of active LN, especially in patients in whom conventional serological and biochemical markers do not appear helpful.
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Affiliation(s)
- Susan Yung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Tak Mao Chan
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
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Yu KY, Yung S, Chau MK, Tang CS, Yap DY, Tang AH, Ying SK, Lee CK, Chan TM. Clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with lupus nephritis. Lupus 2021; 30:1039-1050. [PMID: 33765901 DOI: 10.1177/09612033211004727] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE We investigated the clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with biopsy-proven Class III/IV±V lupus nephritis (LN). METHODS Serum VCAM-1 and ICAM-1 levels were determined by ELISAs. Sera from patients with non-renal SLE or non-lupus chronic kidney disease (CKD), and healthy subjects served as controls. RESULTS Seropositivity rate for VCAM-1 and ICAM-1 was 93.10% and 37.93% respectively at the time of nephritic flare, and 44.83% and 13.79% respectively at remission, with both showing higher levels during flare (P < 0.05, for both). VCAM-1 level correlated with proteinuria, serum creatinine, and anti-dsDNA antibodies, and inversely correlated with C3. VCAM-1 level also correlated with leukocyte infiltration and fibrinoid necrosis/karyorrhexis scores in active LN kidney biopsies. ICAM-1 level correlated with proteinuria, but not anti-dsDNA or C3, nor histopathological features. VCAM-1 level increased 4.5 months before renal flare, while ICAM-1 increase coincided with flare, and both decreased after treatment. ROC analysis showed that VCAM-1 distinguished active LN from healthy subjects, LN in remission, active non-renal lupus, and CKD (ROC AUC of 0.98, 0.86, 0.93 and 0.90 respectively). VCAM-1 level in combination with either proteinuria or C3 was superior in distinguishing active LN from remission compared to the measurement of individual markers. Serum ICAM-1 level distinguished active LN from healthy subjects and LN patients in remission (ROC AUC of 0.75 and 0.66 respectively), but did not distinguish between renal versus non-renal lupus. ICAM-1 level in combination with markers of endothelial cell activation (syndecan-1, hyaluronan and thrombomodulin) was superior to proteinuria, anti-dsDNA, or C3 in distinguishing active LN from quiescent disease. CONCLUSION Our findings suggest potential utility of serum VCAM-1 and ICAM-1 in clinical management. Monitoring VCAM-1 may facilitate early diagnosis of flare. Combining selected biomarkers may be advantageous in diagnosing active LN. VCAM-1 may have a pathogenic role in renal parenchymal inflammation in active LN.
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Affiliation(s)
- Kelvin Yc Yu
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Susan Yung
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Mel Km Chau
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Colin So Tang
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Desmond Yh Yap
- Department of Medicine, The University of Hong Kong, Hong Kong
| | | | - Shirley Ky Ying
- Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong
| | | | - Tak Mao Chan
- Department of Medicine, The University of Hong Kong, Hong Kong
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Guo Liu RN, Cheng QY, Zhou HY, Li BZ, Ye DQ. Elevated Blood and Urinary ICAM-1 is a Biomarker for Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis. Immunol Invest 2019; 49:15-31. [PMID: 31298049 DOI: 10.1080/08820139.2019.1624769] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology. Intercellular cell adhesion molecule-1 (ICAM-1) is critical for leukocyte adhesion to endothelium and migration out of blood vessels and thus participates in many autoimmune diseases. Previous studies of blood and urinary ICAM-1 in SLE have yielded inconsistent results.Methods: The following databases were searched for studies that compared blood and/or urinary ICAM-1 in SLE patients vs. healthy control subjects, and/or in SLE with active vs. inactive diseases: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Web of Science. Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using a random-effects model when there was significant heterogeneity (assesses using the Cochrane Q test and I2 statistics), and using a fixed-effects model otherwise. Publication bias was assessed using funnel plot and egger text.Results: The initial screening yielded a total of 1,215 articles; 22 articles (14 reporting blood ICAM-1, 7 reporting urinary ICAM-1 and 1 reporting both) were included in the meta-analysis. In comparison to healthy controls, SLE patients had elevated urinary ICAM-1 (SMD: 0.711; 95% CI: 0.521, 0.901) as well as blood ICAM-1 (SMD: 0.725; 95% CI: 0.385, 1.065). Blood ICAM-1 did not differ significantly between active and inactive SLE (SMD: 0.396; 95% CI: -0.556, 1.347).Conclusion: Elevated blood and urinary ICAM-1 is a biomarker for SLE, but does not differentiate active and inactive SLE.
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Affiliation(s)
- Run-Nan Guo Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.,Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China
| | - Qian-Yao Cheng
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.,Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China
| | - Hao-Yue Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.,Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China
| | - Bao-Zhu Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.,Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China
| | - Dong-Qing Ye
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China.,Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, China
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Abstract
Mycophenolate mofetil (MMF) has been reproducibly shown to inhibit lymphocyte adhesion and penetration of endothelial cell surfaces. The mechanism is not yet elucidated. In vitro studies on the effects of MMF on cell adhesion molecules (CAM) using human umbilical vein endothelial cells (HUVEC) have shown conflicting results. Different studies have independently shown that MMF increased, decreased or had no effect on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1). Several studies suggest MMF may reduce the endothelial expression of E-selectin. Recent studies have been unable to replicate initial work, which suggested that MMF impaired glycosylation of lymphocyte CAM. The same studies concluded that MMF had no effect on the surface expression of lymphocyte CAM, but altered the binding ability of these molecules. ICAM-1/LFA-1 (lymphocyte function-associated antigen-1), VCAM-1/VLA-4 (very late antigen-4) and P-selectin/PSGL-1 (P-selectin glycoprotein ligand-1) ligand pairs are most likely to be involved. Few in vivo and no conclusive human studies have been carried out. The literature relevant to cell adhesion molecules in systemic lupus erythematosus (SLE) is reviewed in detail.
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Affiliation(s)
- MJ Lewis
- Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London, UK
| | - D D'cruz
- Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, London, UK
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Abstract
Mycophenolate mofetil (MMF) has been reproducibly shown to inhibit lymphocyte adhesion and penetration of endothelial cell surfaces. The mechanism is not yet elucidated. In vitro studies on the effects of MMF on cell adhesion molecules (CAM) using human umbilical vein endothelial cells (HUVEC) have shown conflicting results. Different studies have independently shown that MMF increased, decreased or had no effect on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1). Several studies suggest MMF may reduce the endothelial expression of E-selectin. Recent studies have been unable to replicate initial work, which suggested that MMF impaired glycosylation of lymphocyte CAM. The same studies concluded that MMF had no effect on the surface expression of lymphocyte CAM, but altered the binding ability of these molecules. ICAM-1/LFA-1 (lymphocyte function-associated antigen-1), VCAM-1/VLA-4 (very late antigen-4) and P-selectin/PSGL-1 (P-selectin glycoprotein ligand-1) ligand pairs are most likely to be involved. Few in vivo and no conclusive human studies have been carried out. The literature relevant to cell adhesion molecules in systemic lupus erythematosus (SLE) is reviewed in detail.
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Affiliation(s)
- M J Lewis
- The Rayne Institute, St Thomas' Hospital, London, UK.
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Kyurkchiev D, Bochev I, Ivanova-Todorova E, Mourdjeva M, Oreshkova T, Belemezova K, Kyurkchiev S. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 2014; 6:552-570. [PMID: 25426252 PMCID: PMC4178255 DOI: 10.4252/wjsc.v6.i5.552] [Citation(s) in RCA: 462] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 08/20/2014] [Accepted: 09/10/2014] [Indexed: 02/06/2023] Open
Abstract
According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells (MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.
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Steyers CM, Miller FJ. Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci 2014; 15:11324-49. [PMID: 24968272 PMCID: PMC4139785 DOI: 10.3390/ijms150711324] [Citation(s) in RCA: 327] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2014] [Revised: 05/23/2014] [Accepted: 06/06/2014] [Indexed: 12/13/2022] Open
Abstract
Chronic inflammatory diseases are associated with accelerated atherosclerosis and increased risk of cardiovascular diseases (CVD). As the pathogenesis of atherosclerosis is increasingly recognized as an inflammatory process, similarities between atherosclerosis and systemic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel diseases, lupus, psoriasis, spondyloarthritis and others have become a topic of interest. Endothelial dysfunction represents a key step in the initiation and maintenance of atherosclerosis and may serve as a marker for future risk of cardiovascular events. Patients with chronic inflammatory diseases manifest endothelial dysfunction, often early in the course of the disease. Therefore, mechanisms linking systemic inflammatory diseases and atherosclerosis may be best understood at the level of the endothelium. Multiple factors, including circulating inflammatory cytokines, TNF-α (tumor necrosis factor-α), reactive oxygen species, oxidized LDL (low density lipoprotein), autoantibodies and traditional risk factors directly and indirectly activate endothelial cells, leading to impaired vascular relaxation, increased leukocyte adhesion, increased endothelial permeability and generation of a pro-thrombotic state. Pharmacologic agents directed against TNF-α-mediated inflammation may decrease the risk of endothelial dysfunction and cardiovascular disease in these patients. Understanding the precise mechanisms driving endothelial dysfunction in patients with systemic inflammatory diseases may help elucidate the pathogenesis of atherosclerosis in the general population.
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Affiliation(s)
- Curtis M Steyers
- Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
| | - Francis J Miller
- Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.
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Kim K, Brown EE, Choi CB, Alarcón-Riquelme ME, Kelly JA, Glenn SB, Ojwang JO, Adler A, Lee HS, Boackle SA, Criswell LA, Alarcón GS, Edberg JC, Stevens AM, Jacob CO, Gilkeson GS, Kamen DL, Tsao BP, Anaya JM, Guthridge JM, Nath SK, Richardson B, Sawalha AH, Kang YM, Shim SC, Suh CH, Lee SK, Kim CS, Merrill JT, Petri M, Ramsey-Goldman R, Vilá LM, Niewold TB, Martin J, Pons-Estel BA, Vyse TJ, Freedman BI, Moser KL, Gaffney PM, Williams A, Comeau M, Reveille JD, James JA, Scofield RH, Langefeld CD, Kaufman KM, Harley JB, Kang C, Kimberly RP, Bae SC. Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries. Ann Rheum Dis 2012; 71:1809-14. [PMID: 22523428 PMCID: PMC3466387 DOI: 10.1136/annrheumdis-2011-201110] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin α(M) (complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. METHODS The authors examined several markers in the ICAM1-ICAM4-ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case-control study of 17 481 unrelated participants from four ancestry populations. The single-marker association and gene-gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. RESULTS The A-allele of ICAM1-ICAM4-ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (OR(meta)=1.16, 95% CI 1.11 to 1.22; p=4.88×10(-10) and OR(meta)=1.67, 95% CI 1.55 to 1.79; p=3.32×10(-46), respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91×10(-5)). CONCLUSION These findings are the first to suggest that an ICAM-integrin-mediated pathway contributes to susceptibility to SLE.
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Affiliation(s)
- Kwangwoo Kim
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
| | - Elizabeth E Brown
- Departments of Medicine and Epidemiology, Schools of Medicine and Public Health, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Chan-Bum Choi
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
| | - Marta E Alarcón-Riquelme
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
- Area of Human DNA Variability, Centro de Genómica e Investigación Oncológica (GENYO), Pfizer-Universidad de Granada-Junta de Andalucía, Granada, Spain
| | - Jennifer A Kelly
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Stuart B Glenn
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Joshua O Ojwang
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Adam Adler
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Hye-Soon Lee
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
| | - Susan A Boackle
- Division of Rheumatology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
| | - Lindsey A Criswell
- Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, California, USA
| | - Graciela S Alarcón
- Departments of Medicine and Epidemiology, Schools of Medicine and Public Health, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jeffrey C Edberg
- Departments of Medicine and Epidemiology, Schools of Medicine and Public Health, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Anne M Stevens
- University of Washington, Seattle Children’s Hospital, Seattle, Washington, USA
| | - Chaim O Jacob
- The Lupus Genetic Group, University of Southern California, Los Angeles, California, USA
| | - Gary S Gilkeson
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Diane L Kamen
- Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Betty P Tsao
- David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Juan-Manuel Anaya
- Center for Autoimmune Diseases Research, Universidad del Rosario, Bogota, Colombia
| | - Joel M Guthridge
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Swapan K Nath
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Bruce Richardson
- Division of Rheumatology, University of Michigan and US Department of Veterans Affairs Medical Center, Ann Arbor, Michigan, USA
| | - Amr H Sawalha
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
- Department of Medicine, US Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA
| | - Young Mo Kang
- Department of Internal Medicine (Rheumatology), Kyungpook National University School of Medicine, Daegu, Korea
| | - Seung Cheol Shim
- Division of Rheumatology, Department of Medicine, Eulji Medi-Bio Research Institute, Eulji University, Daejeon, Korea
| | - Chang-Hee Suh
- Department of Rheumatology, Ajou University School of Medicine, Suwon, Korea
| | - Soo-Kon Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Chang-sik Kim
- Department of Ophthalmology, Chungnam National University School of Medicine, Daejeon, Korea
| | - Joan T Merrill
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Michelle Petri
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Luis M Vilá
- Department of Medicine University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Timothy B Niewold
- Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois, USA
| | - Javier Martin
- Department of Immunology, Instituto de Biomedicina y Parasitología López-Neyra, CSIC, Granada, Spain
| | | | - Timothy J Vyse
- King’s College London, Divisions of Genetics and Molecular Medicine and Immunology, Infection and Inflammatory Disease, Guy’s Hospital, London, UK
| | - Barry I Freedman
- Departments of Biostatistical Sciences and Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Kathy L Moser
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Patrick M Gaffney
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
| | - Adrienne Williams
- Departments of Biostatistical Sciences and Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Mary Comeau
- Departments of Biostatistical Sciences and Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - John D Reveille
- Division of Rheumatology, The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Judith A James
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - R Hal Scofield
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
| | - Carl D Langefeld
- Departments of Biostatistical Sciences and Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Kenneth M Kaufman
- Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
- Department of Medicine, US Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA
| | - John B Harley
- Pediatrics and US Department of Veterans Affairs Medical Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA
| | - Changwon Kang
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
| | - Robert P Kimberly
- Departments of Medicine and Epidemiology, Schools of Medicine and Public Health, The University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Sang-Cheol Bae
- Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea
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Akhter E, Burlingame RW, Seaman AL, Magder L, Petri M. Anti-C1q antibodies have higher correlation with flares of lupus nephritis than other serum markers. Lupus 2011; 20:1267-74. [PMID: 21813587 DOI: 10.1177/0961203311411597] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
OBJECTIVE Autoantibodies are important in the diagnosis and classification of systemic lupus erythematosus (SLE), but whether they correlate with changes in disease activity within individual patients is controversial. We assessed the association between changes in SLE global and renal activity and changes in several autoantibodies and cell adhesion molecules in patients with SLE. METHODS Stored sera collected at two or three clinic visits from each of 49 SLE patients (91% female, 59% African-American, 31% Caucasian, 10% other ethnicity, 38% under 30 years, 41% between 30-44 years, and 21% 45-63 years) were analyzed. The visits were chosen to include one visit with proteinuria, and one or two without, for each patient. Global disease activity was measured by the Physician's Global Assessment (PGA), SELENA-SLEDAI (SLE Disease Activity Index modified to exclude anti-dsDNA and complement) and renal activity assessed by urine protein (by urine dipstick) and Renal Activity Score. Sera were assayed for anti-C1q, anti-chromatin, anti-dsDNA, anti-ribosomal P, monocyte chemotactic protein-1 (MCP-1), vascular cell adhesion molecule (VCAM) intercellular adhesion molecule (ICAM) and complement. The associations between changes in disease activity and changes in biomarker levels were assessed. RESULTS In terms of global disease activity, anti-C1q had the highest association with the PGA (p = 0.09) and was strongly associated with modified SELENA-SLEDAI (p = 0.009). In terms of renal activity, anti-C1q had the highest association with proteinuria (p = 0.079), and was strongly associated with Renal Activity Score (p = 0.006). CONCLUSION Anti-C1q performed the best of the potential biomarkers, being significantly associated with the modified SELENA-SLEDAI and with the Renal Activity Score. This study indicates the potential superior utility of anti-C1q over anti-dsDNA and other measures to track renal activity.
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Affiliation(s)
- E Akhter
- Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Illei GG, Tackey E, Lapteva L, Lipsky PE. Biomarkers in systemic lupus erythematosus: II. Markers of disease activity. ACTA ACUST UNITED AC 2004; 50:2048-65. [PMID: 15248202 DOI: 10.1002/art.20345] [Citation(s) in RCA: 111] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Gabor G Illei
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, DHHS, Bethesda, Maryland 20892, USA.
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Foltyn VN, Golan TD. In vitro ultraviolet irradiation induces pro-inflammatory responses in cells from premorbid SLE mice. Lupus 2001; 10:272-83. [PMID: 11341104 DOI: 10.1191/096120301680416968] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in which sunlight (especially its ultraviolet radiation (UVR)) is known to induce exacerbation of cutaneous lesions as well as systemic manifestations of the disease. The aim of this in vitro study was to investigate whether UVR (UVA, UVB) amplifies pro-inflammatory factors in cultured dermal fibroblasts (DF) or lymph node cells derived from premorbid or morbid mice from the murine SLE strains (MRL-1pr/1pr, (NZB/NZW)F1), in comparison to cells derived from normal mice from the non-SLE strains (C57BL/6, BALB/c). Our results demonstrate the following. Dermal fibroblast of premorbid SLE mice showed increased susceptibility to UVA and UVB irradiation, determined by viability assay, in comparison to those of normal mice. UVB irradiation induced an enhanced expression of ICAM-1 in such SLE derived cells, in comparison to cells of normal mice. UVA and UVB increased functional activity of LFA-1 in lymph node cells of premorbid SLE mice and not in normal controls. UVB irradiation induced increased production and secretion of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) in DF of premorbid SLE mice, in comparison to normal controls. The enhanced pro-inflammatory responses to UVR were also observed in experiments conducted with cells derived from morbid SLE mice. In conclusion, the pro-inflammatory proneness detected in the premorbid stage of murine SLE could be of major importance in SLE pathogenesis. Furthermore, it suggests that the autoimmune inflammatory process in vivo, triggered initially by immune complex deposition, could be further amplified by UVR.
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Affiliation(s)
- V N Foltyn
- Department of Immunology, Faculty of Medicine Technion, POB 9649, Haifa IL-31096, Israel.
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