Genomic dissection of immune-mediated disease: a new biology of clinical outcome in autoimmunity? (#138)
The course taken by a given autoimmune or inflammatory disease varies greatly between individuals. From a patient’s perspective, the impact of this long-term prognosis can be more important than the specific diagnosis they are given. We investigated the pathways that control clinical outcome in patients with Crohn’s disease, ulcerative colitis, ANCA-associated vasculitis and SLE. We found transcriptional changes in CD8 T cells that implicated T cell exhaustion in this process and that led to a prognostic test entering clinical practice. Moreover the genetic variants driving outcome were not associated with susceptibility: the biology underlying long-term disease outcome, or prognosis, appears distinct from that driving specific diagnosis, and represents an under-investigated but clinically relevant aspect of disease pathogenesis.