Expanding the B Cell-Centric View of Systemic Lupus Erythematosus.pdfVIP

TREIMM 1364 No. of Pages 10 Review Expanding the B Cell-Centric View of Systemic Lupus Erythematosus Peter A. Morawski1 and Silvia Bolland1,* Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a breakdown of self-tolerance in B cells and the production of antibodies against nuclear self-antigens. Increasing evidence supports the notion that additional cellular contributors beyond B cells are important for lupus pathogenesis. In this review we consider recent advances regarding both the pathogenic and the regulatory role of lymphocytes in SLE beyond the production of IgG autoantibodies. We also discuss various in?ammatory effector cell types involved in cytokine production, removal of self-antigens, and responses to autoreactive IgE antibodies. We aim to integrate these ideas to expand the current understanding of the cellular components that contribute to disease progression and ultimately help in the design of novel, targeted therapeutics. Heterogeneity of SLE SLE is a multiorgan autoimmune disorder with an evident but complex heritable component [1,2]. It is caused by a dysregulation of the immune system that results in chronic in?ammatory disease directed against self-tissue. The molecular and cellular drivers of this dysregulation, as well as the target organs of this misdirected immune response, can be variable, thus explaining the heterogeneity in pathological manifestations. SLE is almost always associated with the presence of serum autoantibodies, supporting the view that a defect in tolerance to common self-antigens is at the center of this disease. The complexity of the genetics of SLE, together with the heterogeneous symptomatic presentation, complicates the task of understanding the causes and triggers of the associated autoimmune pathology. Finding a common pathological mechanism has been elusive and so far only general immunosuppressive drugs seem to be markedly effective in the treatment of SLE [3]. Current advances aim to p