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Báo cáo y học: "B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: B-lymphocyte stimulator/a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin. | Dillon et al. Arthritis Research Therapy 2010 12 R48 http arthritis-research.eom content 12 2 R48 RESEARCH ARTICLE Open Access B-lymphocyte stimulator a proliferation-inducing ligand heterotrimers are elevated in the sera of patients with autoimmune disease and are neutralized by atacicept and B-cell maturation antigen-immunoglobulin 1 1 1 11 1 Stacey R Dillon Brandon Harder Kenneth B Lewis Margaret D Moore Hong Liu Thomas R Bukowski 1 1111 1 Nels B Hamacher Megan M Lantry Mark Maurer Cecile M Krejsa Jeff L Ellsworth Susan Pederson Keith B Elkon2 Mark H Wener2 Maria Dall Era3 Jane A Gross 1 Abstract Introduction B-lymphocyte stimulator BLyS and a proliferation-inducing ligand APRIL are members of the tumor necrosis factor TNF family that regulate B-cell maturation survival and function. They are overexpressed in a variety of autoimmune diseases and reportedly exist in vivo not only as homotrimers but also as BLyS APRIL heterotrimers. Methods A proprietary N-terminal trimerization domain was used to produce recombinant BLyS APRIL heterotrimers. Heterotrimer biologic activity was compared with that of BLyS and APRIL in a 4-hour signaling assay by using transmembrane activator and CAML interactor TACI -transfected Jurkat cells and in a 4-day primary human B-cell proliferation assay. A bead-based immunoassay was developed to quantify native heterotrimers in human sera from healthy donors n 89 and patients with systemic lupus erythematosus SLE n 89 or rheumatoid arthritis RA n 30 . Heterotrimer levels were compared with BLyS and APRIL homotrimer levels in a subset of these samples. Results The recombinant heterotrimers consisted mostly of one BLyS and two APRIL molecules. Heterotrimer signaling did not show any significant difference compared with APRIL in the TACI-Jurkat assay. Heterotrimers were less-potent inducers of B-cell proliferation than were homotrimeric BLyS or APRIL EC50 nMol L BLyS 0.02 APRIL 0.17 heterotrimers 4.06 . The soluble receptor fusion proteins .