Biomarkers of B cell activation in autoimmune connective tissue diseases: more than markers of disease activity

B cells play a central role in the pathogenesis of many autoimmune diseases, acting as antigen-presenting cells, producing inflammatory cytokines, and acting as a source of autoantibodies after differentiating into plasma cells. In this review, we aim to summarize and synthesize the literature for the utility of biomarkers of B cell activation (plasma immunoglobulins (Ig), free light chains (FLCs), and beta-2 microglobulin (β2M)) in monitoring inflammatory rheumatic connective tissue diseases, such as Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), dermatomyositis (DM), and systemic sclerosis (SSc). Clinically, it is quite difficult to gauge prognosis in these conditions as there, historically, have not been many quantitative markers of disease activity available. From our extensive literature review, Ig, FLC, and β2M may function as invaluable prognostic markers of ongoing disease activity, and potentially as biomarkers for response to therapy or disease relapse. They are inexpensive and unsophisticated tests that are vastly underused in the setting of autoimmune disease. However, clinicians still need to be aware of the potential of false positives in times of infection or plasma cell dyscrasia, as these disease states can artificially increase these biomarkers. Ultimately, the utility of serum Ig, FLCs, and β2M is clearly delineated in SS and SLE, and least investigated in DM, and additional prospective studies utilizing these biomarkers, and specific B cell targeted therapies are still needed.