Fc-binding proteins enhance autoantibody-induced BP180 depletion in pemphigoid
Fc-binding proteins enhance autoantibody-induced BP180 depletion in pemphigoid
复制标题
Fc 结合蛋白增强类天疱疮中自身抗体诱导的 BP180 耗竭
作者：
Iwata H;Kamaguchi M;Ujiie H;Ujiie I;Natsuga K;Nishie W;ShimizuH:
免疫球蛋白 (Igs) 由两个抗原结合区 (Fab) 和一个恒定区 (Fc) 组成。蛋白 A 和蛋白 G 是细菌蛋白，因其与 Fc 片段的高亲和力而用于纯化 IgG。类风湿因子是针对 IgG Fc 片段的自身抗体，在生理条件下存在于体内。关于 Fc 结合蛋白对抗体诱导的自身免疫性疾病致病性的影响知之甚少。类天疱疮疾病是一组自身免疫性表皮下水疱性疾病，包括大疱性类天疱疮和粘膜类天疱疮。已知靶向 180 kDa 大疱性类天疱疮抗原 (BP180) 的非胶原 NC16A 结构域的 IgG 会导致小鼠皮肤脆性和角质形成细胞中 BP180 的消耗。在这项研究中，发现针对 NC16A 的 mAb 与 Fc 结合蛋白结合可增强 BP180 的消耗。尽管针对 BP180 C 末端的 mAb 在体内或体外均未表现出致病性，但使用 Fc 结合蛋白处理 mAb 明显诱导小鼠皮肤脆性和角质形成细胞中 BP180 的消耗。抗 BP180 mAb 和 Fc 结合蛋白共定位于细胞质和基底膜区域。细胞粘附强度随着 BP180 量的增加而降低。临床上，大疱性类天疱疮患者的类风湿因子滴度高于对照组。抗 BP180 mAb 与高滴度类风湿因子血清联合使用可增强 BP180 的消耗。此外，粘膜类天疱疮患者的唾液中细菌和 Fc 结合蛋白的含量高于对照组。我们的结果表明，Fc 结合蛋白（类风湿因子或蛋白 G）可能增强类天疱疮疾病中自身抗体的致病性。版权所有 © 2018 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Immunoglobulins (Igs) consist of two antigen‐binding regions (Fab) and one constant region (Fc). Protein A and protein G are bacterial proteins used for the purification of IgG by virtue of their high affinities for the Fc fragment. Rheumatoid factors are autoantibodies against IgG Fc fragments, which are present in the body under physiological conditions. Little is known about the influence of Fc‐binding proteins on the pathogenicity of antibody‐induced autoimmune diseases. Pemphigoid diseases are a group of autoimmune subepidermal blistering disorders that includes bullous pemphigoid and mucous membrane pemphigoid. IgGs targeting the non‐collagenous NC16A domain of the 180‐kDa bullous pemphigoid antigen (BP180) are known to induce skin fragility in mice and the depletion of BP180 in keratinocytes. In this study, mAb against NC16A in combination with Fc‐binding proteins was found to enhance BP180 depletion. Although mAb against the C‐terminus of BP180 does not show pathogenicityin vivoorin vitro, mAb treatment with Fc‐binding proteins clearly induced skin fragility in mice and BP180 depletion in keratinocytes. Anti‐BP180 mAbs and Fc‐binding proteins were colocalized in the cytoplasm and at the basement membrane zone. Cell adhesion strengths were decreased in parallel with BP180 amounts. Clinically, bullous pemphigoid patients had higher rheumatoid factor titers than controls. Anti‐BP180 mAb in combination with high‐titer rheumatoid factor serum was found to enhance BP180 depletion. Furthermore, saliva from mucous membrane pemphigoid patients contained larger quantities of bacteria and Fc‐binding proteins than controls. Our results suggest that Fc‐binding proteins (rheumatoid factor or protein G) may enhance the pathogenicity of autoantibodies in pemphigoid diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.