Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis

Chen, Y. S., Yan, W., Geczy, C. L., Brown, Matthew A, & Thomas, R. (2009) Serum levels of soluble receptor for advanced glycation end products and of S100 proteins are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in rheumatoid arthritis. Arthritis Research and Therapy, 11(2).

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Abstract

Introduction:

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptor molecules. High concentrations of three of its putative proinflammatory ligands, S100A8/A9 complex (calprotectin), S100A8, and S100A12, are found in rheumatoid arthritis (RA) serum and synovial fluid. In contrast, soluble RAGE (sRAGE) may prevent proinflammatory effects by acting as a decoy. This study evaluated the serum levels of S100A9, S100A8, S100A12 and sRAGE in RA patients, to determine their relationship to inflammation and joint and vascular damage.

Methods:

Serum sRAGE, S100A9, S100A8 and S100A12 levels from 138 patients with established RA and 44 healthy controls were measured by ELISA and compared by unpaired t test. In RA patients, associations with disease activity and severity variables were analyzed by simple and multiple linear regressions.

Results:

Serum S100A9, S100A8 and S100A12 levels were correlated in RA patients. S100A9 levels were associated with body mass index (BMI), and with serum levels of S100A8 and S100A12. S100A8 levels were associated with serum levels of S100A9, presence of anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF). S100A12 levels were associated with presence of ACPA, history of diabetes, and serum S100A9 levels. sRAGE levels were negatively associated with serum levels of C-reactive protein (CRP) and high-density lipoprotein (HDL), history of vasculitis, and the presence of the RAGE 82Ser polymorphism.

Conclusions:

sRAGE and S100 proteins were associated not just with RA inflammation and autoantibody production, but also with classical vascular risk factors for end-organ damage. Consistent with its role as a RAGE decoy molecule, sRAGE had the opposite effects to S100 proteins in that S100 proteins were associated with autoantibodies and vascular risk, whereas sRAGE was associated with protection against joint and vascular damage. These data suggest that RAGE activity influences co-development of joint and vascular disease in rheumatoid arthritis patients.

Impact and interest:

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ID Code: 87864
Item Type: Journal Article
Refereed: Yes
Additional Information: No file attached.
Keywords: advanced glycation end product receptor, calgranulin A, cyclic citrullinated peptide antibody, protein S 100, protein S 100A12, protein S 100A9, rheumatoid factor, unclassified drug, advanced glycosylation end product receptor, advanced glycosylation end-product receptor, autoantibody, calgranulin B, immunoglobulin receptor, S100A12 protein, human, adolescent, adult, aged, antibody production, article, body mass, cardiovascular disease, comorbidity, controlled study, diabetes mellitus, disease activity, disease severity, female, human, inflammation, joint destruction, major clinical study, male, rheumatoid arthritis, risk factor, vasculitis, arthropathy, blood, blood vessel, enzyme linked immunosorbent assay, immunology, middle aged, pathology, Aged, 80 and over, Arthritis, Rheumatoid, Autoantibodies, Blood Vessels, Enzyme-Linked Immunosorbent Assay, Humans, Joint Diseases, Receptors, Immunologic, Risk Factors, S100 Proteins, Young Adult
DOI: 10.1186/ar2645
ISSN: 1478-6354
Divisions: Current > Schools > School of Biomedical Sciences
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 29 Sep 2015 04:34
Last Modified: 22 Aug 2016 04:47

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