Revisiting B cell tolerance and autoantibodies in seropositive and seronegative autoimmune rheumatic disease (AIRD)

Autoimmune rheumatic diseases (AIRD) are categorized as seropositive or seronegative, based on the presence or absence of a defined set of autoantibodies. Autoantibodies in AIRD are produced after loss of B cell tolerance, as a consequence of defects incurred during early B cell development, genetic variants in products regulating B and T cell peripheral tolerance, environmental factors, or immunologic triggers. Emerging evidence now suggests that AIRD that were previously considered seronegative do have autoreactive B cells and autoantibodies that contribute to disease.