HLA-A and HLA-DRB1 may play a unique role in ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis

Xiaoya Zhao,Hang Qi,Xiangjun Chen,Bo Deng,Juan Li,Guiling Liang,Chenfeng Zhu,Qian Zhu,Jian Zhang,Wei Xia,Xiaoqing He

doi:10.1186/s12958-020-00661-5

Abstract

BackgroundOvarian 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.MethodsOvarian 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.ResultsIn 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.ConclusionOur investigation indicated that HLA-A and HLA-DRB1 might be involved in mediating ovarian teratoma-associated NMDAR-E. These findings provide new insights into the pathophysiological mechanisms and provide information for the functional exploration of proteins in the future.

Highlights

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
The workflow of this study was as follows: proteins were extracted from the collected samples, which was followed by quality control and proteomic analysis of eight samples using Isobaric tag for relative and absolute quantitation (iTRAQ) quantification proteomics
The results showed that the numbers of human leukocyte antigen (HLA) Class I A (HLA-A) (+) and HLA-DRB1 (+) cells in the Discussion Ovarian teratoma (OT)-associated NMDAR-E is a serious and potentially fatal autoimmune synaptic encephalitis that commonly occurs in young women, and gynecologists often lack relevant experience with the disease [9, 31, 32]

Summary

Introduction

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. 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. Shu et al reported that the HLA class II allele DRB1*16:02 was associated with an increased risk of NMDAR-E in the Chinese Han population [16]. These allele studies highlight the possible association between HLA alleles and NMDAR-E and note that T cells may be involved in pathogenesis [17]

Results

Discussion

Conclusion