B and T cell immune responses in rheumatoid arthritis and myositis In search for the immunological drummers and dancers

The presence of autoantibodies and the association between HLA alleles and the risk for the development of rheumatoid arthritis (RA) and myositis supports a role for B and T cells in the pathogenesis of both disorders. Despite the presence of various treatment regimens, joint destruction in the case of RA and muscle damage in myositis is inevitable. Therefore, there is a need for a better understanding of the disease pathophysiology to identify novel and better therapeutic targets. In this thesis, we aimed to unravel changes in the B and T cell repertoires during the pre(clinical) stages of RA. In addition, we investigated changes in the TCRβ repertoire in peripheral blood and muscle tissues of myositis patients, but we also looked at the effects of IVIg treatment on the BCRH repertoire in treatment-naïve myositis patients. We found changes in the T cell response in lymphoid tissues of RA-risk and RA individuals, shown by altered levels of follicular T cells as well as clonal expansion of the T cell repertoire. Additionally, AIRR-seq of the B and T cell repertoires in muscle biopsies of myositis patients showed signs of an antigen-driven response in muscle tissues, as we found that the B and T cell repertoires in muscle tissues were more expanded and less diverse than the repertoires observed in peripheral blood. Finally, we also showed that the baseline clonal expansion of the peripheral blood BCRH cloud be useful clinically as a marker to stratify which myositis patients will benefit from IVIg treatment.