451 E. Health Sciences Drive, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA 95616, United States.
Autoimmun Rev. 2014 Feb;13(2):163-77. doi: 10.1016/j.autrev.2013.10.005. Epub 2013 Oct 21.
IgA is the most abundant immunoglobulin in the human body, and performs a very specialized role which involves mucosal immunity, development of tolerance and protection against infection. IgA is the key immunoglobulin in the respiratory and gastrointestinal tracts, which provide the most intimate interface between the environment and self. Normal levels of IgA are based on early studies consisting of only small numbers of patients. The international consensus definition of IgA deficiency is a level of 0.07g/l after the age of four years in the absence of IgG and IgM deficiencies. The epidemiology of IgA deficiency reveals interesting variances between geographical regions - the incidence in Caucasians being much higher than that in Asians. IgA deficiency has also been found to co-exist with autoimmune diseases, allergies and malignancies. The association with autoimmunity is particularly interesting because it suggests a common genetic linkage that could potentially also explain the diversity in geoepidemiology. Both MHC and non-MHC associations have been described and the 8.1 haplotype has been significantly associated with autoimmunity in IgA deficiency patients over controls. Non-MHC genetic associations include IFIH1 and CLEC16A. The mutations leading to IgA deficiency have not been defined, but in some cases of IgA deficiency it has been suggested that the pathogenesis involves a failure in switched memory B cells that can lead to this cohort experiencing an increased incidence of recurrent bacterial infections or autoimmune diseases. Attempts to investigate the role of cytokines that can induce IgA synthesis in cells of patients with IgA deficiency, such as IL21 or the combination of CD40L/anti-CD40, IL-4 and IL10, are underway.
IgA 是人体内最丰富的免疫球蛋白，具有非常特殊的作用，涉及黏膜免疫、耐受的发展和抗感染。IgA 是呼吸道和胃肠道的关键免疫球蛋白，为环境与自身之间提供最密切的界面。正常的 IgA 水平基于仅包含少数患者的早期研究。在不存在 IgG 和 IgM 缺乏的情况下，国际共识定义的 IgA 缺乏症的标准为 4 岁以后的血清 IgA 水平<0.07g/L。IgA 缺乏症的流行病学揭示了地理区域之间有趣的差异 - 白种人的发病率明显高于亚洲人。已经发现 IgA 缺乏症与自身免疫性疾病、过敏和恶性肿瘤共存。与自身免疫的关联特别有趣，因为它表明存在共同的遗传联系，这也可能解释地理流行病学的多样性。已经描述了 MHC 和非 MHC 关联，并且在 IgA 缺乏症患者中，8.1 单倍型与自身免疫的关联明显高于对照组。非 MHC 遗传关联包括 IFIH1 和 CLEC16A。导致 IgA 缺乏症的突变尚未确定，但在某些 IgA 缺乏症的情况下，已经提出发病机制涉及到转换记忆 B 细胞的失败，这可能导致这一组患者经历复发性细菌感染或自身免疫性疾病的发生率增加。正在尝试研究可以诱导 IgA 合成的细胞因子（如 IL21 或 CD40L/抗 CD40、IL-4 和 IL10 的组合）在 IgA 缺乏症患者中的作用。
