Emergence of proinflammaotry autoreactive T-cell responses in preclinical rheumatoid arthritis
Before the onset of clinically apparent disease, the pathogenesis of RA goes through a number of sequential phases. The presence of autoimmunity through RF and ACPAs can be detected up to 13 years before the onset of clinical synovitis. An important component of the immune system is Treg cells which limit damage caused by excessive immune activity. These cells have been found to be dysfunctional in RA. This study aimed to identify autoreactive T cells to a known RA-associated antigen and determine the quality of their response. Autoreactive responses were measured in three groups; healthy controls, patients with preclinical RA and patients with RA. The quality of the responses differed between these groups. Health was associated with an IL-10 response but moving into the preclinical RA and RA groups there was an emergence of IFN-? responses. There was a sequential reduction in the ratio of these responses, with disease state having a significant effect on these ratios. Significant differences in the response ratios of IL-10:IFN-? from health to preclinical and health to RA. The authors also found that IL-10 responses actively inhibit IFN-? responses and therefore it is possible that if the IL-10 regulatory responses were upregulated in patients with preclinical RA disease progression could be prevented.