Elevated serum and synovial fluid TNF-like ligand 1A (TL1A) is associated with autoantibody production in patients with rheumatoid arthritis

Abstract

Objectives: Tumour necrosis factor (TNF)-like ligand 1A (TL1A) is involved in rheumatoid arthritis (RA) but its clinical relevance in RA has not been fully elucidated. We analysed TL1A levels in the serum and synovial fluid (SF) of RA patients and investigated its clinical significance.

Methods: TL1A levels were measured by enzyme-linked immunosorbent assay (ELISA) in 109 RA patients, 29 patients with osteoarthritis (OA), and 126 healthy controls. Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin G (RF-IgG) were tested by ELISA. RF-IgM, anti-keratin antibody (AKA), and anti-perinuclear factor (APF) antibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulins were measured by standard laboratory techniques. The associations between TL1A and the clinical and serological features of RA were analysed.

Results: TL1A concentrations were significantly elevated in both serum and SF of RA patients compared with OA patients and healthy controls. TL1A levels in RA SF were significantly higher than those in matched serum. A positive correlation was found between SF and serum TL1A levels. Serum TL1A concentrations were associated with RA-specific autoantibodies including RFs (RF-IgG, RF-IgM) and anti-citrullinated protein antibodies. Antibody production by peripheral blood mononuclear cells (PBMCs) from RA patients was elevated upon TL1A stimulation. However, there was no correlation between serum or SF TL1A levels and RA disease activity.

Conclusions: TL1A levels are significantly elevated in RA serum and SF and positively correlated with autoantibody production in RA, but failed as a disease activity marker. TL1A promotes antibody production by PBMCs from RA patients. The role of TL1A in the humoral autoimmune response may be important in the development of RA.

Acknowledgements

This work was supported by grant 81172847 and 31000409 of the National Natural Science Foundation of China, Beijing Natural Science Foundation (7123233), the National Basic Research Programme of China (973 programme, 2010CB529100), China Postdoctoral Science Foundation the First Class (2012M510073) and Nanjing Young Medical Talent Project.