Cytokine expression and cytokine-based T cell profiling in South Indian rheumatoid arthritis

Rheumatoid arthritis (RA), a chronic inflammatory disease affects up to 1% of the general population. Early diagnosis and treatment are limited by the absence of specific and reliable diagnostic/prognostic biomarkers. This study was carried out in 48 Tamil South Indian RA patients and 49 healthy controls (HC) to identify any cytokine signature(s) that could potentially serve as biomarkers. Expression profiles of Th1, Th2, Th17 and Tregs cell type-specifying cytokines and transcription factors were analyzed using real time quantitative PCR (qPCR) assay. To explore if such expression profiles mirror their steady state plasma levels, a bead-based multiplex fluorescent assay was carried out. We found that the expression of transcription factors T-bet (for Th1), GATA-3 (for Th2) and FoxP3 (for Tregs) were significantly lower in patients than in healthy controls (P<0.0001) similar to lowering of IFNγ (P=0.004) and IL-10 (P=0.04). The transcript levels of IL-12p40 and TNF-α were higher among patients as compared to HC (P<0.0001 and P=0.02, respectively). Circulating levels of assessed cytokines were in general higher in RA patients as compared to controls. These alterations in the expression of transcription factors and cytokines highlight the underlying dysregulation of T cell subsets in RA that reflects a predominantly inflammatory phenotype. Despite dissecting these cellular and molecular processes, no specific signature that could be of diagnostic and/or prognostic value was identified. Additional longitudinal follow-up studies, especially on newly diagnosed treatment-naïve patients are warranted to uncover clinically useful biomarkers of RA.