State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Dermatology Hospital of Jiangxi Province, Jiangxi Provincial Clinical Research Center for Skin Diseases, Candidate Branch of National Clinical Research Center for Skin Diseases, Dermatology Institute of Jiangxi Province, The Affiliated Dermatology Hospital of Nanchang University, Nanchang, China.
Front Immunol. 2022 Jun 1;13:903174. doi: 10.3389/fimmu.2022.903174. eCollection 2022.
Mucous membrane pemphigoid (MMP) and anti-laminin (LM) γ1 pemphigoid, two subtypes of subepidermal autoimmune bullous diseases characterized by autoantibodies against epidermal basement membrane zone proteins, mainly show mucosal and skin lesions, respectively. The known autoantigens of MMP includes BP180, BP230, LM332, integrin α6β4 and type VII collagen, and anti-LMγ1 pemphigoid targets LMγ1. In this study, we present an unique MMP case with oral mucosal lesions, which showed positive IgA signals on basement membrane zone in indirect immunofluorescence using normal human skin and on dermal side in indirect immunofluorescence using salt-split skin, positive IgA autoantibodies against LMγ1 by immunoblotting of epidermal extracts, positive IgA autoantibodies against LMα5 by immunoblotting of LM521 recombinant protein (rLM521) and positive IgG autoantibodies against LMγ1 by immunoblotting of rLM111 and rLM521 at first visit (Day 0). After therapy, further serological analyses of serum samples collected at Day 30 and Day 50 indicated that IgA autoantibodies against LMγ1 were likely to be pathogenic. These results suggest that LMγ1 is another autoantigen of MMP, and our patient might be the first reported case of anti-LMγ1 MMP.
黏膜性类天疱疮(Mucous membrane pemphigoid,MMP)和抗层粘连蛋白(Laminin,LM)γ1 类天疱疮,是两种以表皮基底膜带蛋白自身抗体为特征的亚表皮自身免疫性大疱病亚型,分别主要表现为黏膜和皮肤损害。MMP 的已知自身抗原包括 BP180、BP230、LM332、整合素α6β4 和 VII 型胶原,而抗-LMγ1 类天疱疮的靶抗原为 LMγ1。在本研究中,我们报告了一例独特的 MMP 病例,该患者口腔黏膜病变,间接免疫荧光法使用正常人体皮肤时在基底膜带呈现 IgA 信号,使用盐裂皮肤时在真皮侧呈现 IgA 信号,表皮提取物的免疫印迹显示 IgA 自身抗体针对 LMγ1 阳性,LM521 重组蛋白(rLM521)的免疫印迹显示 IgA 自身抗体针对 LMα5 阳性,rLM111 和 rLM521 的免疫印迹显示 IgG 自身抗体针对 LMγ1 阳性,这些均在初次就诊(第 0 天)时发现。治疗后,第 30 天和第 50 天采集的血清样本的进一步血清学分析表明,针对 LMγ1 的 IgA 自身抗体可能具有致病性。这些结果表明,LMγ1 是 MMP 的另一个自身抗原,我们的患者可能是首例报道的抗-LMγ1 MMP 病例。