The role of B cells in giant cell arteritis and polymyalgia rheumatica

Giant cell arteritis (GCA) is an inflammatory vascular disease (vasculitis) affecting cranial arteries, aorta and its major branches in people older than 50 years of age. GCA frequently overlaps with polymyalgia rheumatica (PMR) which is characterized by inflammation of the shoulder- and hip girdle. Despite immunosuppressive treatment with glucocorticoids (GC), inflammation often persists in these diseases necessitating long-term treatment with considerable side effects (GC toxicity). Novel and improved treatment options are therefore highly needed.
Research on the immunopathogenesis of GCA/PMR has been focussed on T cells and macrophages. The B cells have long been neglected due to the lack of specific auto-antibodies and the limited presence of B cells in temporal artery biopsies. Beside differentiating into antibody secreting cells, B cells can also contribute to autoimmune diseases via pro-inflammatory cytokine production. This thesis aimed to explore the role of B cells in the pathogenesis of GCA and PMR with a focus on cytokine production. We propose a disease model where B cells contribute to disease by fuelling inflammation. This is based on observation of infiltrating B cells which organize into tertiary lymphoid structures (TLOs) in affected arteries, especially the aorta. These B cells can produce chemokines and cytokines. After in vitro stimulation circulating B cells also produce several pro-inflammatory cytokines which are capable of polarizing macrophages towards a pro-inflammatory and tissue destructive phenotype. Our findings suggest that B cells might be an interesting target for treatment to interfere with disease chronicity in patients with GCA/PMR.