Study of B Cell Repertoire in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.
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SUBMITTER: Feng J
PROVIDER: S-EPMC7403192 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Autoimmune encephalitis (AE) covers a group of neurological diseases caused by autoantibodies. AE is severe but treatable. It has attracted more and more attention currently. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common AE characterized by specific autoantibody mainly against NMDAR subunit 1. Cell-based assays (CBA) on human embryonic kidney 293 (HEK293) cells and immunohistochemistry (IHC) on rat brain tissue have been widely used to detect antibody in patients with AE. However, few studies focused on the overview of these assays detecting autoantibodies in AE. Here we reviewed the detection assays in AE and compared the sensitivity and specificity of CBA and IHC. It's found that IHC got a higher positive rate than CBA in both serum and cerebrospinal fluid (CSF) when screening potential AE, while CBA was more specific. Besides, more positive samples were found in CSF than in serum by either IHC or CBA. Hence, both serum and CSF should be sent to detect antibodies by two assays to avoid misdiagnosis. CSF antibody titers were believed more clinically relevant. When positive results were shown in IHC but negative in CBA, other kinds of antibodies associated AE instead of anti-NMDAR encephalitis should be taken into account. Further studies should pay attention to serum testing for diagnosis or assessment of the disease, as CSF testing is invasive and not always available.
| S-EPMC10116423 | biostudies-literature
Project description:Objective: The aim of this retrospective study was to investigate the relationship between serum systemic autoantibodies and anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: Thirty-nine patients with anti-NMDAR encephalitis were examined for serum systemic autoantibodies (antinuclear antibodies, extractable nuclear antigen autoantibodies, rheumatoid factors, and anti-neutrophil cytoplasmic antibodies), in comparison with 39 neuromyelitis optica spectrum disorder (NMOSD) and 78 healthy controls. Clinical features, cerebrospinal fluid characteristics, and outcomes were compared between the two subgroups of anti-NMDAR patients with positive and negative systemic autoantibodies, respectively. Results: Anti-NMDAR encephalitis patients had higher frequency of positive serum systemic autoantibodies than healthy controls (23.1 vs. 2.6%, p = 0.001) and lower frequency than NMOSD (23.1 vs. 48.7%, p = 0.018). No patients were diagnosed comorbidities with non-organ-specific autoimmune diseases. Consciousness disturbance was more frequent in autoantibodies positive group than in the negative group (88.9 vs. 40.0%, p = 0.02). Autoantibody positive group had a poorer outcome than autoantibody negative group (55.6 vs. 86.7%, p = 0.043). There was a negative correlation between serum autoantibodies and outcomes in anti-NMDAR encephalitis patients (r = -0.325, p = 0.044). Conclusion: Our data demonstrated serum systemic autoantibodies were more frequent in anti-NMDAR encephalitis patients than in healthy controls and less frequent than NMOSD, which were associated with higher severity of disease.
| S-EPMC7059175 | biostudies-literature
Project description:PurposeWe 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.MethodsWe 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.ResultsCompared 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).ConclusionSerum D-dimer and neutrophil levels were independent predictors of disease severity in patients with first-attack anti-NMDAR encephalitis.
| S-EPMC9707621 | biostudies-literature
Project description:ObjectiveTo investigate factors that could impact or predict the probability of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis recurrence in central China.MethodsFrom November 2014 to October 2020, observational data of anti-NMDAR encephalitis inpatients in our institution were collected and analyzed prospectively. The demographics, clinical characteristics, tumor status, lesion locations on MRI and immunotherapies, etc. had entered into a Cox regression model for the identification of the factors associated with relapse-free survival.ResultsWe enrolled 113 patients in a row (median age: 28 years, range: 1-61 years). The gender distribution was not statistically significant (p = 0.158), with 49 people (43.4%) being female. The median follow-up time was 16 (4-77) months. Among them, 16.8% of patients relapsed. The average interval between recurrences was 8 months (range 3-54 mo). The severity of the initial relapse was less severe than it had been at the start. The first relapse had considerably fewer symptoms (median 2, range 1-6) than the first episode (median 4, range 1-8, p = 0.005). The mRS at first relapse (median 3, mean 2.84, range 1-5) had been significantly lower than that at onset (median 4, mean 3.89, range 3-5, p = 0.004). The length of hospitalization at first relapse (median 17 days, range 5-46) was significantly shorter than the first episode (median 35 days, range 14-102, p = 0.002). In the survival analysis, the risk of recurrence was significantly higher for patients with a brainstem lesion (HR: 4.112, 95% CI: 1.205-14.030; p = 0.024) or ≥3 abnormal sites (HR: 2.926, 95% CI: 1.085-7.896; p = 0.034) on brain MRI at the first episode. There was no significant difference in neurological outcomes between the recurrent and monophasic groups at the most recent follow-up (mRS 0-2 in 17/19 vs. 86/94; p = 0.674).ConclusionsAnti-NMDAR encephalitis can recur in around one out of every six cases, and symptoms are generally milder than when it first appears. Recurrence is not related to the severity in the acute phase or the prognosis at follow-up. Patients with ≥3 abnormal sites on MRI or lesions located in the brainstem at onset must be alert to the possibility of recurrence.
| S-EPMC8959942 | biostudies-literature
Project description:OBJECTIVE:To report the autoantigens of a new category of treatment-responsive paraneoplastic encephalitis. METHODS:Analysis 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). RESULTS:Twelve 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. INTERPRETATION:Antibodies 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.
| S-EPMC2430743 | biostudies-literature
Project description:To report the clinical features of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in patients < or = 18 years old.Information was obtained by the authors or referring physicians. Antibodies were determined by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) using HEK293 cells ectopically expressing NR1.Over an 8-month period, 81 patients (12 male) with anti-NMDAR encephalitis were identified. Thirty-two (40%) were < or =18 years old (youngest 23 months, median 14 years); 6 were male. The frequency of ovarian teratomas was 56% in women >18 years old, 31% in girls < or =18 years old (p = 0.05), and 9% in girls < or =14 years old (p = 0.008). None of the male patients had tumors. Of 32 patients < or =18 years old, 87.5% presented with behavioral or personality change, sometimes associated with seizures and frequent sleep dysfunction; 9.5% with dyskinesias or dystonia; and 3% with speech reduction. On admission, 53% had severe speech deficits. Eventually, 77% developed seizures, 84% stereotyped movements, 86% autonomic instability, and 23% hypoventilation. Responses to immunotherapy were slow and variable. Overall, 74% had full or substantial recovery after immunotherapy or tumor removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma (4/23; p = 0.03).Anti-NMDAR encephalitis is increasingly recognized in children, comprising 40% of all cases. Younger patients are less likely to have tumors. Behavioral and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children. Ann Neurol 2009;66:11-18.
| S-EPMC2826225 | biostudies-literature
Project description:Objectives: The function of the N-methyl-D-aspartate receptor (NMDAR) in the kidney has been studied. However, the effect on the kidney from anti-NAMDAR antibody encephalitis has not been investigated thus far. Methods: Case data were collected from 82 patients with anti-NMDAR antibody encephalitis and 166 age- and sex-matched healthy controls (HCs). Clinical characteristics, urinalysis [including urine pH and urine specific gravity (SG)], serum creatinine (Scr), and estimated glomerular filtration rate (eGFR) based on Cr levels were evaluated. Results: At initial admission, urine pH levels and urine SG levels in anti-NMDAR antibody encephalitis patients were significantly higher and lower, respectively, than HCs (both p < 0.001). There were no significant differences in Scr and eGFR between anti-NMDAR antibody encephalitis patients and HCs. Urine pH levels in patients with anti-NMDAR antibody <1:32 were significantly lower than those in patients with anti-NMDAR antibody ≥1:32 (p = 0.029). Urine pH levels were significantly lower (p = 0.004) and urine SG levels were significantly higher (p = 0.027) in a follow-up evaluation 3 months after treatment. Conclusions: The changes in urinalysis occur in patients with anti-NMDAR antibody encephalitis. The pathophysiological changes in anti-NMDAR antibody encephalitis were not limited to the CNS.
| S-EPMC7907499 | biostudies-literature
Project description:ObjectiveMovement disorders (MDs) are common in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis but are poorly studied. This study aimed to investigate the clinical characteristics of MDs and the clinical differences between patients with and without MDs in anti-NMDAR encephalitis.MethodsA retrospective study was conducted on patients with anti-NMDAR encephalitis who were first diagnosed and treated in the First People's Hospital of Yunnan Province from January 2017 to September 2022. According to the presence or absence of MDs, all patients were divided into two groups, and the clinical manifestations, auxiliary examinations, and prognosis of the two groups were compared. Patients in the MDs group were further subgrouped by different ages (<12 years, 12-17 years, and ≥ 18 years) and genders, and the prevalence of each MD was compared in different age and gender groups.Results(1) In our study there were 64 patients, of whom 76.6% (49/64) presented with MDs; the median age of onset in patients with MDs was 21 (15,35) years and 65.3% (32/49) were female. The three most common MDs were orofacial dyskinesia (OFLD) (67.3%), dystonia (55.1%), and stereotypies (34.7%). Patients <12 years were more likely to experience chorea than patients in other age groups (p = 0.003). (2) Compared with the non-MDs group, patients in the MDs group showed higher rates of prodromal manifestations, autonomic dysfunction, consciousness disorders, as well as pulmonary infection and gastrointestinal dysfunction (all p < 0.05). Peripheral blood neutrophil to lymphocyte ratio (NLR) (p = 0.014), the proportion of cerebrospinal fluid (CSF) NMDAR antibody titers ≥1:32 (p = 0.047), ICU admission rate (p = 0.04), length of stay (p = 0.007), maximum mRS score in the course of disease (p = 0.001) and mRS score at discharge (p = 0.006) in the MDs group were significantly higher than the non-MDs group.ConclusionMDs associated with anti-NMDAR encephalitis were predominantly hyperkinetic. Chorea occurred more commonly in patients aged <12 years. Patients with MDs were prone to autonomic dysfunction, consciousness disorders, pulmonary infection, and gastrointestinal dysfunction; they had more intense inflammation, more severe disease, and a poorer short-term prognosis.
| S-EPMC10941647 | biostudies-literature
Project description:ObjectiveSeizures develop in 80% of patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, and these represent a major cause of morbidity and mortality. Anti-NMDAR antibodies have been linked to memory loss in encephalitis; however, their role in seizures has not been established. We determined whether anti-NMDAR antibodies from autoimmune encephalitis patients are pathogenic for seizures.MethodsWe performed continuous intracerebroventricular infusion of cerebrospinal fluid (CSF) or purified immunoglobulin (IgG) from the CSF of patients with anti-NMDAR encephalitis or polyclonal rabbit anti-NMDAR IgG, in male C57BL/6 mice. Seizure status during a 2-week treatment was assessed with video-electroencephalography. We assessed memory, anxiety-related behavior, and motor function at the end of treatment and assessed the extent of neuronal damage and gliosis in the CA1 region of hippocampus. We also performed whole-cell patch recordings from the CA1 pyramidal neurons in hippocampal slices of mice with seizures.ResultsProlonged exposure to rabbit anti-NMDAR IgG, patient CSF, or human IgG purified from the CSF of patients with encephalitis induced seizures in 33 of 36 mice. The median number of seizures recorded in 2 weeks was 13, 39, and 35 per mouse in these groups, respectively. We observed only 18 brief nonconvulsive seizures in 11 of 29 control mice (median seizure count of 0) infused with vehicle (n = 4), normal CSF obtained from patients with noninflammatory central nervous system (CNS) conditions (n = 12), polyclonal rabbit IgG (n = 7), albumin (n = 3), and normal human IgG (n = 3). We did not observe memory deficits, anxiety-related behavior, or motor impairment measured at 2 weeks in animals treated with CSF from affected patients or rabbit IgG. Furthermore, there was no evidence of hippocampal cell loss or astrocyte proliferation in the same mice.SignificanceOur findings indicate that autoantibodies can induce seizures in anti-NMDAR encephalitis and offer a model for testing novel therapies for refractory autoimmune seizures.
| S-EPMC6684284 | biostudies-literature
Project description:BackgroundAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis responds to immunnotherapy, and approximately 80% of patients with this disorder fully recover or have only minor sequelae. Brain magnetic resonance imaging (MRI) does not show a specific abnormality, but some patients have progressive cerebral atrophy. The cerebral atrophy can become reversible after clinical improvement.MethodsWe describe 3 patients with diffuse cerebral atrophy (DCA) on serial brain MRI.ResultsTwo women had the typical spectrum of this disorder, and one man had mainly psychiatric symptoms. In a woman with an ovarian tumor, DCA was reversible and DCA developed within about a half month. In another woman without a tumor, DCA was evident within 19 days and had progressed over the course of 4 years. The titers of anti-NMDAR antibodies in serum and cerebrospinal fluid (CSF) initially decreased, and low titers of the antibodies persisted. In a man without a tumor, DCA progressed within 14 days, and during this short period, he did not receive prolonged treatment with corticosteroids, various antiepileptic agents, or propofol, and he was free of seizures and ventilatory support.ConclusionNot only a woman but also a man with anti-NMDAR encephalitis can have DCA in the early phase of this disorder. However, DCA can be reversible after clinical improvements. The early progression of DCA is not necessarily a poor prognostic factor.
| S-EPMC5413277 | biostudies-literature