The immunological basis of B-cell therapy in systemic lupus erythematosus.
Loss of B-cell tolerance is a hallmark feature of the pathogenesis in systemic lupus erythematosus (SLE), an autoimmune disease that is characterized by hypergammaglobulinemia and autoantibody production. These autoantibodies lead to formation of immune-complex deposition in internal organs causing inflammation and damage. Autoreactive B-cells are believed to be central in the pathophysiology of SLE. Other than its role in the production of antibodies that mediate humoral immune response, B-cells also function as antigen-presenting cells and are capable of activating T-cells. Activated B-cells may also produce pro-inflammatory cytokines that aggravate local inflammation. Abnormal B-cell homeostasis has been described in SLE patients. This may occur as a result of intrinsic B-cell defect or from aberrant regulation by maturation and survival signals. B-cell-based therapy is the current mainstream of research and development of novel therapies in SLE patients with severe and refractory disease. Potential cellular and molecular targets for B-cell therapies include cell surface molecules such as CD20 (rituximab) and CD22 (epratuzumab); co-stimulatory molecules involved in B-cell-T-cell interaction such as CTLA4 and B7 molecules (abatacept); maturation and growth factors such as B-cell activating factor and a proliferation-inducing ligand (belimumab, briobacept, atacicept) and B-cell tolerogen (abetimus). This article provides an overview on normal B-cell physiology and abnormal B-cell biology in SLE that form the immunological basis of B-cell-targeted therapy in the treatment of these patients with refractory diseases.
Mok
Mo Yin
MY
Division of Rheumatology & Immunology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong. temy@hkucc.hku.hk
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy / Q000379:methods; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001323:Autoantibodies; D016207:Cytokines