Some viruses can accelerate the development of autoimmune diseases in certain individuals. In this issue, we discuss the hypothesis that certain viruses impair immune tolerance. As one example, we discuss the relationship between rheumatoid arthritis (RA) and Epstein-Barr virus (EBV). EBV is well known to be associated with African Burkitt's B cell lymphoma, nasopharyngeal carcinoma and infectious mononucleosis. EBV has also been implicated in the pathogenesis of RA, based on indirect evidence, such as the presence of EBV particles in affected joint tissues, antigenic cross reactions between EBV and human proteins, and elevated humoral and cellular anti-EBV immune responses in patients. Since EBV plays an important role in polyclonal B cell activation, this virus might be associated with autoimmune dysfunction in patients with RA. We cloned the SAP/SH2D1A (signaling lymphocytic-activation molecule associated protein/Src homology 2 domain-containing protein) gene from peripheral leukocytes of patients with IgA nephropathy. SAP is essential for late B cell responsiveness, the development of long-term humoral immunity and the induction of cytotoxic T cells against EBV; it may also be involved in the regulation of the pathogenesis of RA. In the patients, expression of the SAP gene was decreased in the peripheral T cells that are thought to play critical roles, in conjunction with cytotoxic T cells and natural killer cells, in the elimination of EBV-infected B cells. Humanized mice (NOD/Shi-scid/IL-2Rã null (NOG) mice transplanted with CD34 + hematopoietic stem cells) were inoculated with EBV and examined pathologically for signs of arthritis; erosive arthritis accompanied by synovial membrane proliferation, pannus formation and bone marrow edema were observed. These findings strongly suggest a causative role of EBV in RA.
Anti-complement component C5 therapy (Eculizumab) utilizes a humanized monoclonal antibody that is a terminal complement inhibitor. Eculizumab was developed and was approved by the United States Food and Drug Administration (FDA) in 2007 for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and in 2011 for the treatment of atypical hemolytic uremic syndrome (aHUS). Eculizumab inhibits the cleavage of C5 to C5a and C5b by the C5 convertase, which prevents the generation of the terminal complement complex C5b-9 (and also exhibits prothrombotic and proinflammatory effects). Both C5a and C5b-9 cause the terminal complementmediated events that are characteristic of aHUS. By inhibiting the complement cascade at this point, the normal, disease-preventing functions of the proximal complement system are largely preserved, while the properties of C5 that promote inflammation and cell destruction are impeded. We present a review of the role of anti-complement component C5 therapy (Eculizumab) in aHUS patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.