CCR6+ Th cell distribution differentiates systemic lupus erythematosus patients based on anti-dsDNA antibody status

Abstract

Background. Systemic lupus erythematosus (SLE) disease has been shown to be associated with the generation of multiple auto-antibodies. Among these, anti-dsDNA antibodies (anti-DNAs) are specific and play a pathogenic role in SLE. Indeed, anti- DNA+ SLE patients display a worse disease course. The generation of these pathogenic anti-DNAs has been attributed to the interaction between aberrant T helper (Th) cells and autoimmune B cells. Thus, in this study we have investigated whether CCR6+ Th cells have the ability to differentiate SLE patients based on anti-DNA status, and if their distribution has any correlation with disease activity. Methods. We recruited 25 anti-DNAC and 25 anti-DNA- treatment-naive onset SLE patients, matched for various clinical characteristics in our nested matched case-control study. CCR6C Th cells and their additional subsets were analyzed in each patient by flow cytometry. Results. Anti-DNAC SLE patients specifically had a higher percentage of Th cells expressing CCR6 and CXCR3. Further analysis of CCR6C Th cell subsets showed that anti-DNAC SLE patients had elevated proportions of Th9, Th17, Th17.1 and CCR4/CXCR3 double-negative (DN) cells. However, the proportions of CCR6- Th subsets, including Th1 and Th2 cells, did not show any association with anti-DNA status. Finally, we identified a correlation between CCR6C Th subsets and clinical indicators, specifically in anti-DNA+ SLE patients. Conclusions. Our data indicated that CCR6C Th cells and their subsets were elevated and correlated with disease activity in anti-DNAC SLE patients. We speculated that CCR6C Th cells may contribute to distinct disease severity in anti-DNAC SLE patients.