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抗微生物抗体、宿主免疫与自身免疫性疾病

Anti-microbial Antibodies, Host Immunity, and Autoimmune Disease.

作者信息

Zhang Peilin, Minardi Lawrence M, Kuenstner J Todd, Zekan Steven M, Kruzelock Rusty

机构信息

PZM Diagnostics, LLC, Charleston, WV, United States.

WV Regional Technology Park, South Charleston, WV, United States.

出版信息

Front Med (Lausanne). 2018 May 23;5:153. doi: 10.3389/fmed.2018.00153. eCollection 2018.

Abstract

Autoimmune diseases are a spectrum of clinical inflammatory syndromes with circulating autoantibodies. Autoimmune diseases affect millions of patients worldwide with enormous costs to patients and society. The diagnosis of autoimmune diseases relies on the presence of autoantibodies and the treatment strategy is to suppress the immune system using specific or non-specific immunosuppressive agents. The discovery of anti-microbial antibodies in the blood of patients with Crohn's disease and Sjogren's syndrome and cross-reactivity of anti-microbial antibodies to human tissue suggests a new molecular mechanism of pathogenesis, raising the possibility of designing a new therapeutic strategy for these patients. The presence of anti-microbial antibodies indicates the failure of the innate immunity system to clear the microbial agents from the blood and activation of adaptive immunity through B-lymphocytes/plasma cells. More importantly, the specific antibodies against the microbial proteins are directed toward the commensal microbes commonly present on the surface of the human host, and these commensal microbes are important in shaping the development of the immune system and in maintaining the interaction between the human host and the environment. Persistence of these anti-microbial antibodies in patients but not in normal healthy individuals suggests abnormal interaction between the human host and the commensal microbes in the body. Elimination of the organism/organisms that elicits the antibody response would be a new avenue of therapy to investigate in patients with autoimmune diseases.

摘要

自身免疫性疾病是一系列伴有循环自身抗体的临床炎症综合征。自身免疫性疾病影响着全球数百万患者,给患者和社会带来了巨大的成本。自身免疫性疾病的诊断依赖于自身抗体的存在,治疗策略是使用特异性或非特异性免疫抑制剂来抑制免疫系统。在克罗恩病和干燥综合征患者血液中发现抗微生物抗体以及抗微生物抗体与人组织的交叉反应提示了一种新的发病分子机制,增加了为这些患者设计新治疗策略的可能性。抗微生物抗体的存在表明先天免疫系统未能从血液中清除微生物病原体,并通过B淋巴细胞/浆细胞激活了适应性免疫。更重要的是,针对微生物蛋白的特异性抗体针对的是通常存在于人类宿主表面的共生微生物,而这些共生微生物在塑造免疫系统发育以及维持人类宿主与环境之间的相互作用方面很重要。这些抗微生物抗体在患者而非正常健康个体中持续存在,提示人体宿主与体内共生微生物之间存在异常相互作用。消除引发抗体反应的一种或多种生物体将是在自身免疫性疾病患者中进行研究的一条新的治疗途径。

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