HLA-A and HLA-DRB1 may play a unique role in ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis
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(2020) 18:107
RESEARCH
Open Access
HLA-A and HLA-DRB1 may play a unique role in ovarian teratoma-associated anti-Nmethyl-D-aspartate receptor encephalitis Xiaoya Zhao1†, Juan Li2†, Qian Zhu1, Guiling Liang1, Wei Xia1, Xiaoqing He1, Chenfeng Zhu1, Hang Qi1, Bo Deng3, Xiangjun Chen3* and Jian Zhang1*
Abstract Background: Ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune neurological disorder, and the influence of teratoma-induced autoantibodies on the pathogenesis remains unclear. Methods: Ovarian teratoma tissues were collected from teratoma patients with and without NMDAR-E. Proteins were extracted and then analyzed using iTRAQ-coupled LC–MS/MS, which was followed by bioinformatics analysis. Candidate proteins were verified by Western blotting and immunohistochemistry. Results: In total, 36 differentially expressed proteins (DEPs) were identified between the control group and NMDAR-E group, and the bioinformatics analysis revealed that the DEPs were mainly involved in immune-related pathways, especially HLA-A and HLA-DRB1. The western blotting results for HLA-A and HLA-DRB1 were consistent with the results of the iTRAQ analysis. Additionally, the immunohistochemical data revealed that the aggregation of HLA-A (+) and HLA-DRB1 (+) cells was more apparent in the teratoma tissues of NMDAR-E patients compared with that in the tissues of controls. Conclusion: Our investigation indicated that HLA-A and HLA-DRB1 might be involved in mediating ovarian teratomaassociated NMDAR-E. These findings provide new insights into the pathophysiological mechanisms and provide information for the functional exploration of proteins in the future. Keywords: Ovarian teratoma, Anti-N-methyl-D-aspartate receptor encephalitis, HLA-A, HLA-DRB1, Autoantibodies
Background Ovarian teratoma (OT) is one of the most common ovarian neoplasms, constituting 10–20% of all ovarian tumors in adults and almost half of all ovarian tumors in children. These tumors originate from three germ layers, namely, the ectoderm, mesoderm, and endoderm [1, 2]. However, * Correspondence: [email protected]; [email protected] † Xiaoya Zhao and Juan Li contributed equally to this work. 3 Department of Neurology, Huashan Hospital and Institute of Neurology, Fudan University, No. 12 Wulumuqi Zhong Road, Shanghai 200040, China 1 Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, No. 910, Hengshan Rd, Shanghai 200030, China Full list of author information is available at the end of the article
women with teratomas might also suffer from anti-Nmethyl-D-aspartate receptor encephalitis (NMDAR-E), a paraneoplastic syndrome that typically results in progressive neuropsychiatric symptoms, hyperkinetic movements, dysautonomia, seizures and autoantibodies against the central nervous system (CNS) [3–7]. NMDAR-E is a recently described severe autoimmune neurological disorder with a progressive clinical course c
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