The purpose of this study was to describe the types of periosteal reaction seen in response to long-standing leg ulcers and to differentiate the types associated with osteomyelitis. Moreover, compared with other IgG isotypes with undesired effector functions, mutant IgG4 Fc should prove useful in constructing novel therapeutic reagents to block immune molecule signalling in various diseases.Ulcer osteoma and periosteal reactions to chronic leg ulcers. Thus, BAFF blockade with BAFF-R-IgG4mut protein is an effective strategy to treat B-cell-mediated lupus-like pathology. Treated mice developed lower proteinuria, reduced glomerulonephritis and much delayed host death than untreated animals. Treatment of BXSB mice with BAFF-R-IgG4mut fusion protein for 5 weeks resulted in significant B-cell reduction in both the peripheral blood and spleen. Mutation of Leu235 to Glu in IgG4 Fc eliminated antibody-dependent cell cytotoxicity (ADCC) and complement lysis activity, and generated a protein devoid of immune effector functions. In this study, we demonstrated the biological outcome of BAFF blockade in BXSB murine lupus model, using a soluble fusion protein consisting of human BAFF-R and human mutant IgG4 Fc. Conclusions: Our data suggested that HCMVpp65336-439 sub-fragment may induce cross-reactive antibodies to several nuclear antigens, which could contribute to the development of autoimmunity in genetic-suspected individuals.ī-cell-activating factor (BAFF), a member of the tumour necrosis factor superfamily, plays a critical role in the maturation, homeostasis and function of B cells. Immunoglobulin deposition on glomeruli was also detected on pp65336-439-immunized mice. Yeast two-hybrid analyses revealed the binding of pp65336-439 sub-fragment to cellular proteins. The immunization of pp65336-439 induced formation of multiple anti-nuclear antibodies, including anti-chromatin, anti-centriole, anti- mitotic spindle type I/II (MSA I/II) and a significant elevation of anti-double-stranded DNA (anti-dsDNA) antibodies on BALB/c mice. Of these positive sera, 73% were also positive to the pp65336-439 sub-fragment. Results: Our results showed that most SLE patients possessed antibodies to the C-terminal half of the HCMVpp65 antigen. The interactions between pp65 sub-fragment to cellular proteins were revealed by yeast two-hybrid analyses. The deposition of immunoglobulin to the kidney was also examined by immunofluorescent stain. Methods: Sera from SLE patients or HCMVpp65-immunized mice were analyzed for anti-nuclear antibody by immunoblotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescent stain and Crithidia luciliae stain. This study further examined whether the B cell epitope(s) in pp65 is able to drive the development of autoantibody. Previously we reported that HCMV phosphoprotein 65 (pp65) could induce early onset of autoantibody and glomerulonephritis on lupus-prone NZB/W mice. Introduction: Human cytomegalovirus (HCMV) infection has been implicated in the development of autoimmunity, including systemic lupus erythematosus (SLE). Therefore, IL-10 may play an important role in highly disturbed immune system and B cell-T cell function in these immune disorders. B cell hyperactivity in autoantibody production in SLE and RA may be a function of IL-10-dependent CD4+CD45RO+ Th2 cell activation. Increased IgM and IgG production by B cells-CD4+CD45RO+ T cells in SLE and RA was IL-10 dependent, since neutralization of IL-10 cytokine by anti-IL-10 antibody drastically reduced Ig synthesis in these coculture experiments. B cells and CD4+CD45RO+ “memory” T cells secreted highly enhanced levels of IL-10 in SLE and RA versus normals. IL-10 was detectable in serum of all active SLE and serum and synovial fluid samples of all RA patients but in none of the normal controls. In this study, we have examined the secretion andin vitro function of IL-10 in B cell hyperactivity in antibody production in two common autoimmune diseases, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Interleukin-10 (IL-10) is a major immunoregulatory cytokine and has a multitude of immunomodulatory effects in the immune system.
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