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

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

doi:10.1186/s12958-020-00661-5

Cited by 5 publications

(6 citation statements)

References 46 publications

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“…In terms of laboratory and MRI tests, most patients had positive OCB and anti-NMDAR antibody in serum or cerebrospinal fluid, and all MRI findings were more compatible with MS, although MS and anti-NMDAR encephalitis were not easily distinguishable on MRI (17). Unlike previous reports of anti-NMDAR encephalitis associated with ovarian teratomas (30), none of these 10 patients developed tumors. As far as treatment is concerned, immunotherapy has been the mainstream, with adjuvant symptomatic treatment, but there are differences in the treatment modalities given at different stages of the disease, such as the use of disease modifying drugs in the MS phase.…”

Section: Anti-nmdar Encephalitis and Multiple Sclerosismentioning

confidence: 55%

Case Report: Antibodies to the N-Methyl-D-Aspartate Receptor in a Patient With Multiple Sclerosis

et al. 2021

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The association between multiple sclerosis and anti-N-Methyl-D-Aspartate receptor encephalitis is limited to merely a few case reports, and the exploration of the pathogenic mechanisms underlying the overlap of these two disease entities is very limited. Therefore, case reports and literature review on N-Methyl-D-aspartate receptor antibody in patients with multiple sclerosis are unusual and noteworthy. A young female had the first episode of paresthesia and motor symptoms with positive anti-N-Methyl-D-Aspartate receptor antibody and recovered after immunotherapy, and at the first relapse, the patient developed disorders of consciousness with positive anti-N-Methyl-D-Aspartate receptor antibody, findings of magnetic resonance imaging showed features of autoimmune encephalitis, which was also controlled by immunotherapy. At the second relapse, anti-N-Methyl-D-Aspartate receptor antibody turned negative while oligoclonal bands presented positive, and findings of magnetic resonance imaging showed features of multiple sclerosis. Afterwards, we followed the patient after receiving disease modifying treatment to monitor the efficacy and safety of teriflunomide. Based on literature review, demyelinating diseases patients with anti-neuronal antibody have complex, diverse and atypical symptoms; therefore, high attention and increased alertness are necessary for neurologists. Conclusively, anti-neuronal antibody may present in many neuroinflammatory conditions, and diagnostic criteria should be used with caution if the clinical presentation is atypical, and neurologists should not rely excessively on laboratory tests to diagnose neurological diseases. Timely and comprehensive examination and consideration as well as early standardized treatment are the key factors to reduce patient recurrence and obtain a good prognosis.

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Section: Anti-nmdar Encephalitis and Multiple Sclerosismentioning

confidence: 55%

Case Report: Antibodies to the N-Methyl-D-Aspartate Receptor in a Patient With Multiple Sclerosis

et al. 2021

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“…Our study found significantly higher expression of DEGs related to MHC-II (HLA-DQA2, HLA-DRB5, and HLA-DOB) and MHC-I (HLA-A, HLA-E, and HLA-F) in Bn and Bm cells in NMDAR-E patients' PB compared to the control group. Apart from Zhao et al's report that HLA-A and HLA-DRB1 may be involved in mediating ovarian teratoma-related NMDAR-E, 39 whether these genes undergo changes in NMDAR-E patients has not been explored in other studies. Therefore, these genes require confirmation through multi-center studies and larger sample sizes.…”

Section: Discussionmentioning

confidence: 99%

“…Apart from Zhao et al . 's report that HLA‐A and HLA‐DRB1 may be involved in mediating ovarian teratoma‐related NMDAR‐E, 39 whether these genes undergo changes in NMDAR‐E patients has not been explored in other studies. Therefore, these genes require confirmation through multi‐center studies and larger sample sizes.…”

Section: Discussionmentioning

confidence: 99%

Single‐cell RNA sequencing reveals diverse B cell phenotypes in patients with anti‐NMDAR encephalitis

Li,

Hu,

Wang

et al. 2023

Psychiatry Clin Neurosci

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BackgroundsAnti‐N‐methyl‐D‐aspartate receptor encephalitis (NMDAR‐E) is a severe autoimmune disorder characterized by prominent psychiatric symptoms. Although the role of NMDAR antibodies in the disease has been extensively studied, the phenotype of B cell subsets is still not fully understood.MethodsWe utilized single‐cell RNA sequencing, single‐cell B cell receptor sequencing (scBCR‐seq), bulk BCR sequencing, flow cytometry, and enzyme‐linked immunosorbent assay to analyze samples from both NMDAR‐E patients and control individuals.ResultsThe cerebrospinal fluid (CSF) of NMDAR‐E patients showed significantly increased B cell counts, predominantly memory B (Bm) cells. CSF Bm cells in NMDAR‐E patients exhibited upregulated expression of differential expression genes (DEGs) associated with immune regulatory function (TNFRSF13B and ITGB1), whereas peripheral B cells upregulated DEGs related to antigen presentation. Additionally, NMDAR‐E patients displayed higher levels of IgD−CD27− double negative (DN) cells and DN3 cells in peripheral blood (PB). In vitro, DN1 cell subsets from NMDAR‐E patients differentiated into DN2 and DN3 cells, while CD27+ and/or IgD+B cells (non‐DN) differentiated into antibody‐secreting cells (ASCs) and DN cells. NR1‐IgG antibodies were found in B cell culture supernatants from patients. Differential expression of B cell IGHV genes in CSF and PB of NMDAR‐E patients suggests potential antigen class switching.ConclusionB cell subpopulations in the CSF and PB of NMDAR‐E patients exhibit distinct compositions and transcriptomic features. In vitro, non‐DN cells from NMDAR‐E can differentiate into DN cells and ASCs, potentially producing NR1‐IgG antibodies. Further research is necessary to investigate the potential contribution of DN cell subpopulations to NR1‐IgG antibody production.

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“…Unfortunately, to date, no tumor markers are available to differentiate teratomas that may cause anti-NMDAR encephalitis. Last, although a study found significantly elevated levels of HLA-A and HLA-DBR1 in teratoma tissues from patients with anti-NMDAR encephalitis ( 69 ), the association of both alleles with disease susceptibility was weak and needs confirmation.…”

Section: Neurological Examinationmentioning

confidence: 97%

Ovarian Teratoma-Related Paraneoplastic Neurological Syndromes

Lin

Wang

2022

Front. Oncol.

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Paraneoplastic neurological syndromes (PNSs) are a group of neurological disorders triggered by an underlying remote tumor. Ovarian teratoma (OT) is the most common histologic type of germ cell tumor in females. The most common PNSs associated with OT is anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, with the increasing number of new antibodies reported over the last decade, the clinical spectrum of OT-related PNSs is also expanding. Our knowledge of OT-related PNSs is still far from complete. Here, we provide a comprehensive review of the most recent findings in the field of OT-related PNSs, with a particular focus on their clinical and pathological characteristics. Overall, the description of neuronal antibodies in PNSs associated with OT strongly suggests that antibodies may be responsible for the clinical symptoms in some cases. OT-related PNSs are associated with various clinical manifestations, including anti-NMDAR encephalitis, limbic encephalitis, encephalomyelitis, progressive cerebellar syndrome and opsoclonus-myoclonus syndrome. The pathological characteristics of the OT suggest that the mechanism of PNSs is probably due to heteromorphic neurons in the tumor tissue, the ectopic expression of the antigens in neural tissue within the teratomas and patients’ unusual immune response. Despite the severity of the neurological syndromes, most patients with OT-related PNSs showed good neurologic response to early tumor resection combined with immunotherapy. To further advance the management of OT-related PNSs, additional studies are needed to explore this complex topic.

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

Cited by 5 publications

References 46 publications

Case Report: Antibodies to the N-Methyl-D-Aspartate Receptor in a Patient With Multiple Sclerosis

Case Report: Antibodies to the N-Methyl-D-Aspartate Receptor in a Patient With Multiple Sclerosis

Single‐cell RNA sequencing reveals diverse B cell phenotypes in patients with anti‐NMDAR encephalitis

Ovarian Teratoma-Related Paraneoplastic Neurological Syndromes

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