Dataset Information

Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis.

ABSTRACT:

Purpose

We aimed to explore the difference in coagulation function between healthy individuals and patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its relationship with disease severity.

Methods

We retrospectively compared coagulation function in 161 patients with first-attack anti-NMDAR encephalitis and 178 healthy individuals. The association between D-dimer levels and disease severity was analyzed using binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of D-dimer levels for the severity of anti-NMDAR encephalitis.

Results

Compared to control individuals, patients with anti-NMDAR encephalitis had higher D-dimer levels (median 0.14 vs. 0.05 mg/L, p < 0.001), blood white blood cell (WBC) count (median 8.54 vs. 5.95 × 10⁹/L, p < 0.001), and neutrophil count (median 6.14 vs. 3.1 × 10⁹/L, p < 0.001). D-dimers (median 0.22 vs. 0.10 mg/L, p < 0.001), blood WBC count (median 9.70 vs. 7.70 × 10⁹/L, p < 0.001), neutrophil count (median 7.50 vs. 4.80 × 10⁹/L, p < 0.001), and C-reactive protein (median 2.61 vs. 1.50 mg/l, p = 0.017) were higher; however, eosinophils (median 0.02 vs. 0.06 × 10⁹/L, p < 0.001), and blood calcium (median 2.26 vs. 2.31 mmol/L, p = 0.003) were lower in patients with severe forms of anti-NMDAR encephalitis than in those with mild to moderate forms, and were associated with initial modified Rankin Scale scores. Multivariate analysis showed that D-dimer levels were significantly associated with severity [odds ratio =2.631, 95% confidence interval (CI) = 1.018-6.802, p = 0.046]. The ROC curve was used to analyze the predictive value of D-dimer levels for disease severity. The area under the curve was 0.716 (95% CI = 0.64-0.80, p < 0.001), and the best cut-off value was D-dimer = 0.147 mg/L (sensitivity 0.651; specificity, 0.705).

Conclusion

Serum D-dimer and neutrophil levels were independent predictors of disease severity in patients with first-attack anti-NMDAR encephalitis.

SUBMITTER: Shao Y

PROVIDER: S-EPMC9707621 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Shao Yingzhe Y Du Juan J Song Yajun Y Li Yanfei Y Jing Lijun L Gong Zhe Z Duan Ranran R Yao Yaobing Y Jia Yanjie Y Jiao Shujie S

Frontiers in neurology 20221115

<h4>Purpose</h4>We aimed to explore the difference in coagulation function between healthy individuals and patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its relationship with disease severity.<h4>Methods</h4>We retrospectively compared coagulation function in 161 patients with first-attack anti-NMDAR encephalitis and 178 healthy individuals. The association between D-dimer levels and disease severity was analyzed using binary logistic regression. Receiver operati ...[more]

PMID: 36457866

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Project description:Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a nervous autoimmune disorder discovered in the recent more than fifteen years. To understand potential involvement of epigenetic mechanisms in pathogenesis of anti-NMDAR encephalitis, we initiated a study to compare the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNA (mRNAs) in patients of anti-NMDAR encephalitis and healthy controls. Methods: 11 patients who were diagnosed with anti-NMDAR encephalitis were enrolled in our observational studies. Total RNA was extracted from patients’ plasma and the expression levels of lncRNAs and mRNAswere determined. Differential expression analysis via RNA sequencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as a co-expression network of lncRNA-mRNA were performed in 5 patients and 5 healthy controls to evaluate potential the changes in expression patterns. The expression levels of certain lncRNAs and mRNAs were further validated in 11patients and 11 healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR). Results: It was found that a total of 83 lncRNAs and 2345 mRNAs were differentially expressed in five patients with anti-NMDAR encephalitis compared with five healthy controls. Of those lncRNAs, 63 were upregulated and 20 downregulated, while 1509 mRNAs were upregulated and 836 downregulated. GO and KEGG pathway analyses showed that a wide range of biological functions were perturbed during acute anti-NMDAR encephalitis. Differentially expressed genes were found to be involved in autoimmune, B cell signaling, neuroinflammation, or synaptic plasticity. qRT-PCR was conducted in 11 patients and 11healthy controls to further confirm the levels of six lncRNAs and four mRNAs, and the results were found to be consistent with those by RNA sequencing. The co-expression networks of lncRNA-mRNA were performed in some meaningful KEGG analyses, including chemokine signaling pathway, Long-term potentiation, B cell receptor signaling pathway and MAPK signaling pathway. Conclusions: Taken together, these findings suggest the involvement of a number of molecular pathways in anti-NMDAR encephalitis, some of which could serve as potential biomarkers to assist in diagnosis, treatment and prognosis.

Project description:ObjectiveTo report the autoantigens of a new category of treatment-responsive paraneoplastic encephalitis.MethodsAnalysis of clinical features, neuropathological findings, tumors, and serum/cerebrospinal fluid antibodies using rat tissue, neuronal cultures, and HEK293 cells expressing subunits of the N-methyl-D-aspartate receptor (NMDAR).ResultsTwelve women (14-44 years) developed prominent psychiatric symptoms, amnesia, seizures, frequent dyskinesias, autonomic dysfunction, and decreased level of consciousness often requiring ventilatory support. All had serum/cerebrospinal fluid antibodies that predominantly immunolabeled the neuropil of hippocampus/forebrain, in particular the cell surface of hippocampal neurons, and reacted with NR2B (and to a lesser extent NR2A) subunits of the NMDAR. NR2B binds glutamate and forms heteromers (NR1/NR2B or NR1/NR2A/NR2B) that are preferentially expressed in the adult hippocampus/forebrain. Expression of functional heteromers (not single subunits) was required for antibody binding. Eleven patients had teratoma of the ovary (six mature) and one a mature teratoma in the mediastinum; five of five tumors examined contained nervous tissue that strongly expressed NR2 subunits and reacted with patients' antibodies. Tumor resection and immunotherapy resulted in improvement or full recovery of eight of nine patients (paralleled by decreased antibody titers); two of three patients without tumor resection died of neurological deterioration. Autopsies showed extensive microgliosis, rare T-cell infiltrates, and neuronal degeneration predominantly involving, but not restricted to, the hippocampus.InterpretationAntibodies to NR2B- and NR2A-containing heteromers of the NMDAR associate with a severe but treatment-responsive encephalitis. Our findings provide a diagnostic test and suggest a model of autoimmune NMDAR-related encephalitis with broad implications for other immune-mediated disorders of memory, behavior, and cognition.

Dataset Information

Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Purpose

Methods

Results

Conclusion

Publications

Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis.

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