Targeting plasma cells in systemic autoimmune rheumatic diseases - Promises and pitfalls

Plasma cells are the antibody secretors of the immune system. Continuous antibody secretion over years can provide long-term immune protection but could also be held responsible for long-lasting autoimmunity in case of self-reactive plasma cells. Systemic autoimmune rheumatic diseases (ARD) affect multiple organ systems and are associated with a plethora of different autoantibodies. Two prototypic systemic ARDs are systemic lupus erythematosus (SLE) and Sjögren's disease (SjD). Both diseases are characterized by B-cell hyperactivity and the production of autoantibodies against nuclear antigens. Analogues to other immune cells, different subsets of plasma cells have been described. Plasma cell subsets are often defined dependent on their current state of maturation, that also depend on the precursor B-cell subset from which they derived. But, a universal definition of plasma cell subsets is not available so far. Furthermore, the ability for long-term survival and effector functions may differ, potentially in a disease-specific manner. Characterization of plasma cell subsets and their specificity in individual patients can help to choose a suitable targeting approach for either a broad or more selective plasma cell depletion. Targeting plasma cells in systemic ARDs is currently challenging because of side effects or varying depletion efficacies in the tissue. Recent developments, however, like antigen-specific targeting and CAR-T-cell therapy might open up major benefits for patients beyond current treatment options.