RESEARCH - RAGE and S100 are associated with inflammatory, autoantibody, and classical risk markers of joint and vascular damage in RA

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Arthritis Research & Therapy 2009, 11:R39doi:10.1186/ar2645

Published: 11 Mar 2009

Research article

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

Yueh-Sheng Chen , Weixing Yan , Carolyn L Geczy , A Brown and

Ranjeny

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 pro-inflammatory ligands:

S100A8/A9 complex (calprotectin), S100A8, and S100A12 are found in

rheumatoid arthritis (RA) serum and synovial fluid. In contrast,

soluble receptor for advanced glycation end products (sRAGE) may

prevent pro-inflammatory effects by acting as a decoy. This study

evaluated the serum levels of S100A9, S100A8, S100A12 and soluble

receptor for advanced glycation end products in rheumatoid arthritis

patients, to determine their relationship to inflammation and joint

and vascular damage.

Methods

Serum soluble receptor for advanced glycation end products, S100A9,

S100A8 and S100A12 levels from 138 patients with established

rheumatoid arthritis and 44 healthy controls were measured by ELISA

and compared by unpaired t-test. In rheumatoid arthritis patients,

associations with disease activity and severity variables were

analyzed by simple and multiple linear regression.

Results

Serum S100A9, S100A8 and S100A12 levels were correlated in rheumatoid

arthritis patients. S100A9 levels were associated with body mass

index, 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. S100A12 levels were

associated with presence of anti-citrullinated peptide antibodies,

history of diabetes, and serum S100A9 levels. Soluble receptor for

advanced glycation end products 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

Soluble receptor for advanced glycation end products and S100 proteins

were associated not just with rheumatoid arthritis inflammation and

autoantibody production, but also with classical vascular risk factors

for end-organ damage. Consistent with its role as a receptor for

advanced glycation end products decoy molecule, soluble receptor for

advanced glycation end products had opposing effects to S100 proteins,

in that S100 proteins were associated with autoantibodies and vascular

risk, whereas soluble receptor for advanced glycation end products was

associated with protection against joint and vascular damage. These

data suggest that receptor for advanced glycation end products

activity influences co-development of joint and vascular disease in

rheumatoid arthritis patients.

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Read the full article here:

http://arthritis-research.com/content/pdf/ar2645.pdf

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