Liu Yingzi, Bao Lei, Sodha Dharm, Li Jing, Mansini Adrian, Djalilian Ali R, Li Xiaoguang, Qian Hua, Ishii Norito, Hashimoto Takashi, Amber Kyle T
Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92617, USA.
Department of Dermatology, Rush University Medical Center, Chicago, IL 60612, USA.
Antibodies (Basel). 2024 Nov 14;13(4):91. doi: 10.3390/antib13040091.
: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. : In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. : We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. : oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role.
眼部为主型黏膜类天疱疮（oMMP）是自身免疫性水疱病（AIBD）的一种严重亚型，可导致瘢痕形成和视力丧失。oMMP的诊断具有挑战性，因为通过传统检测方法，患者循环自身抗体水平往往无法检测到。同样，oMMP中的主要自身抗原一直是一个有争议的领域。：在这项初步实验中，我们对oMMP患者以及非眼部MMP、大疱性类天疱疮和黏膜皮肤型寻常型天疱疮患者的血清进行了噬菌体免疫沉淀测序（PhIP-seq）。：我们鉴定出相对于其他AIBD，oMMP特有的几种自身抗原。然后，我们将这些抗原与先前发表的单核数据集以及国际小鼠表型分析联盟数据库进行交叉比对。我们研究中鉴定出的几种蛋白质命中物在前表面上皮细胞上显示出富集表达，包括TNKS1BP1、SEC16B、FNBP4、CASZ1、GOLGB1、DOT1L、PRDM 15、LARP4B和RPL6。同样，先前一项对小鼠类似物CASZ1、HIP1和ELOA2基因敲除模型的研究报告称，这些小鼠在眼表和眼睛发育方面表现出异常。值得注意的是，PhIP-seq未能鉴定出AIBD的典型标志物，如BP180、BP230、桥粒芯糖蛋白1和3或整合素β4，这表明患者自身抗体与构象表位而非线性表位发生反应。：相对于其他AIBD，oMMP患者表现出独特的自身抗体谱。对鉴定出的自身抗体进行进一步验证将有助于揭示它们潜在的致病作用。
