Increased Prevalence of Diverse N-Methyl-D-Aspartate Glutamate Receptor Antibodies in Patients With an Initial Diagnosis of Schizophrenia Specific Relevance of IgG NR1a Antibodies for Distinction From N-Methyl-D-Aspartate Glutamate Receptor Encephalitis
Increased Prevalence of Diverse N-Methyl-D-Aspartate Glutamate Receptor Antibodies in Patients With an Initial Diagnosis of Schizophrenia Specific Relevance of IgG NR1a Antibodies for Distinction From N-Methyl-D-Aspartate Glutamate Receptor Encephalitis
复制标题
DOI：
10.1001/2013.jamapsychiatry.86
复制
发表时间：
2013-03-01
期刊：
影响因子：
25.8
通讯作者：
Stoecker, Winfried
中科院分区：
文献类型：
--
作者：
Steiner, Johann;Walter, Martin;Stoecker, Winfried
内容：精神分裂症和N-甲基-D-天冬氨酸谷氨酸受体（NMDA-R）脑炎症状趋同的证据强调了在精神障碍中的谷氨酸能病理生理异常中诊断为精神分裂症的患者中评估抗体流行率和对不同疾病机制的特异性的需要。目的：比较精神分裂症患者NMDA-R抗体的特异性和患病率（DSM-IV标准）与其他精神病诊断的抗体亚型进行比较，并确定抗体亚型是否与NMDA-R脑炎中的抗体亚型特征重叠和区别。从我们的科学血库中获得了459例急性精神分裂症、重性抑郁症（MD）和边缘型人格障碍（BLPD）患者或作为匹配对照的个体的血清。探讨NMDA-R的抗原表位特异性和抗体亚型，（NR 1a或NR 1a/NR 2b）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体（AMPA-R）（GluR 1/GluR 2）血清抗体测定。将230例匹配的健康对照与患者进行比较，主要结果测量：主要结果是NMDA-R和AMPA-R抗体血清阳性病例的总数;次要结果是伊加/IgG/IgM抗体的疾病特异性和临床亚组的表位特异性。在15名受试者中发现了不同的NMDA-R抗体，主要是那些最初诊断为精神分裂症的受试者（9.9%），而MD（2.8%）、BLPD（0）和对照组（0.4%）。后来，2例最初被归类为紧张性或紊乱性精神分裂症的患者被重新归类为误诊为NMDA-R脑炎（存在特异性血清和脑脊液IgG NR 1a抗体）。在所有其他血清阳性病例中，抗体由伊加和/或IgM类组成，或针对NR 1a/NR 2b（而不是单独针对NR 1a）。没有患者或对照组有抗体对AMPA-R。结论：急性精神分裂症患者的初步诊断显示NMDA-R抗体的患病率增加。精神分裂症和MD的抗体亚型库与NMDA-R脑炎不同。后一种疾病应被视为一种鉴别诊断，特别是在年轻女性急性行为紊乱或紧张症。JAMA精神病学杂志2013; 70（3）：271-278. 2013年1月23日在线发布。doi：10.1001/2013.jamapsychiatry.86
Context: Evidence for symptomatic convergence of schizophrenia and N-methyl-D-aspartate glutamate receptor (NMDA-R) encephalitis highlights the need for an assessment of antibody prevalence and specificity for distinct disease mechanisms in patients with a diagnosis of schizophrenia among glutamatergic pathophysiologic abnormalities in psychiatric disorders.Objectives: To compare the specificity and prevalence of NMDA-R antibodies in schizophrenia (DSM-IV criteria) with those of other psychiatric diagnoses and to determine whether antibody subtypes characterize overlap with and distinction from those in NMDA-R encephalitis.Design: Serum from 459 patients admitted with acute schizophrenia, major depression (MD), and borderline personality disorder (BLPD) or individuals serving as matched controls was obtained from our scientific blood bank. To explore epitope specificity and antibody subtype, IgA/IgG/IgM NMDA-R (NR1a or NR1a/NR2b) and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPA-R) (GluR1/GluR2) serum antibodies were determined.Participants: Two hundred thirty matched healthy controls were compared with patients (unmedicated for at least 6 weeks) with schizophrenia (n=121), MD(n=70), or BLPD (n=38).Main Outcome Measures: The primary outcome was the overall number of seropositive cases for NMDA-R and AMPA-R antibodies; the secondary outcome was disease specificity of IgA/IgG/IgM antibodies and epitope specificity for clinical subgroups.Results: Diverse NMDA-R antibodies were identified in 15 subjects, primarily those with an initial schizophrenia diagnosis (9.9%), opposed to MD (2.8%), BLPD (0), and controls (0.4%). Retrospectively, 2 patients initially classified as having catatonic or disorganized schizophrenia were reclassified as having misdiagnosed NMDA-R encephalitis (presence of specific serum and cerebrospinal fluid IgG NR1a antibodies). In all other seropositive cases, the antibodies consisted of classes IgA and/or IgM or were directed against NR1a/NR2b (not against NR1a alone). None of the patients or controls had antibodies against AMPA-R.Conclusions: Acutely ill patients with an initial schizophrenia diagnosis show an increased prevalence of NMDA-R antibodies. The repertoire of antibody subtypes in schizophrenia andMDis different from that with NMDA-R encephalitis. The latter disorder should be considered as a differential diagnosis, particularly in young females with acute disorganized behavior or catatonia. JAMA Psychiatry. 2013; 70(3): 271-278. Published online January 23, 2013. doi:10.1001/2013.jamapsychiatry.86