Expression and modulation of complement receptor 2 (CR2/CD21) in the pathophysiology of rheumatoid arthritis

Background: The involvement of B cells, complement activation and subsequent immune complex deposition has been implicated in the pathogenesis of rheumatoid arthritis (RA). Although the reduced expression of complement receptor 2 (CR2, CD21) on the B cells of RA patients is known for long, we aimed at determining the modulation and expression of CR2 on PBMC of healthy individuals and RA patients.Methods: Sixty controls and 57 RA patients were enrolled. PBMC-CR2 transcript levels were correlated with the levels of C3, C3d and circulating immune complexes (CIC) in controls and patients and with DAS28 in patients only. CIC levels were determined by PEG precipitation, C3 levels by nephlometry and C3d levels were determined by enzyme linked immunosorbent assay (ELISA). Sixteen patients were recruited for 6 months follow up studies of transcript levels of PBMC correlated with DAS28 score. Appropriate statistical methods were used for the analyses of data.Results: PBMC- CR2 transcript levels were declined in patients as compared to controls. PBMC-CR2 levels correlated negatively with DAS28 score. DAS28 correlated positively with levels of CIC, C3 and C3d. Levels of PBMC -CR2 increased in patients with decline in DAS28 scores in 6 months follow-up patients.Conclusions: Low level of CR2 expression in patients may, thus, contribute significantly to the pathological manifestation of RA. Cause-effect relationships of the up regulation of CR2 on improvement of health condition with the pathophysiology of RA and their importance as putative disease markers is being confirmed.

Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis

Abstract Background Role of Th9 cells and interleukin-9 (IL-9) in human autoimmune diseases such as psoriasis and ulcerative colitis has been explored only very recently. However, their involvement in human rheumatoid arthritis (RA) is not conclusive. Pathogenesis of RA is complex and involves various T cell subsets and neutrophils. Here, we aimed at understanding the impact of IL-9 on infiltrating immune cells and their eventual role in synovial inflammation in RA. Methods In vitro stimulation of T cells was performed by engagement of anti-CD3 and anti-CD28 monoclonal antibodies. Flow cytometry was employed for measuring intracellular cytokine, RORγt in T cells, evaluating apoptosis of neutrophils. ELISA was used for measuring soluble cytokine, Western blot analysis and confocal microscopy were used for STAT3 phosphorylation and nuclear translocation. Results We demonstrated synovial enrichment of Th9 cells and their positive correlation with disease activity (DAS28-ESR) in RA. Synovial IL-9 prolonged the survival of neutrophils, increased their matrix metalloprotienase-9 production and facilitated Th17 cell differentiation evidenced by induction of transcription factor RORγt and STAT3 phosphorylation. IL-9 also augmented the function of IFN-γ + and TNF-α + synovial T cells. Conclusions We provide evidences for critical role of IL-9 in disease pathogenesis and propose that targeting IL-9 may be an effective strategy to ameliorate synovial inflammation in RA. Inhibiting IL-9 may have wider impact on the production of pathogenic cytokines involved in autoimmune diseases including RA and may offer better control over the disease

Additional file 1: Table S1. of Synovial IL-9 facilitates neutrophil survival, function and differentiation of Th17 cells in rheumatoid arthritis

Demographic and clinical characteristics of RA patients (n = 28). (DOCX 12 kb