Systemic lupus erythematosus and its ABCs (APRIL/BLyS complexes).
BLyS and APRIL are closely related members of the TNF ligand superfamily. These cytokines individually may contribute importantly to the development and maintenance of systemic lupus erythematosus (SLE). Dillon and colleagues demonstrate that in contrast to most members of the TNF ligand superfamily, which form only homotrimers, BLyS and APRIL can complex as heterotrimers. These complexes have in vitro biological activity, and circulating levels of BLyS/APRIL heterotrimers are frequently elevated in SLE, but not rheumatoid arthritis, patients. Although the mechanism and regulation of heterotrimer formation, the interconversion (if any) between homotrimers and heterotrimers, and, indeed, the normal physiologic role for such heterotrimers remain unknown, their preferential overexpression in SLE, but not in rheumatoid arthritis, raises the possibility that such heterotrimers may be playing a contributory role in SLE.
Stohl
William
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood* / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D011993:Recombinant Fusion Proteins; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; C511911:belimumab; C524618:TACI receptor-IgG Fc fragment fusion protein