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抗DNA/N-甲基-D-天冬氨酸受体2抗体在初发及类固醇治疗后神经精神性系统性红斑狼疮患者中的临床意义

Clinical significance of anti-DNA/N-methyl-D-aspartate receptor 2 antibodies in de novo and post-steroid cases with neuropsychiatric systemic lupus erythematosus.

作者信息

Fujieda Yuichiro, Mader Simone, Jeganathan Venkatesh, Arinuma Yoshiyuki, Shimizu Yuka, Kato Masaru, Oku Kenji, Minami Akiko, Shimizu Chikara, Yasuda Shinsuke, Atsumi Tatsuya

机构信息

Department of Rheumatology, Endocrinology and Nephrology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Japan.

Center of Autoimmune and Musculoskeletal Diseases, The Feinstein Institute for Medical Research, Manhasset, New York.

出版信息

Int J Rheum Dis. 2019 Mar;22(3):443-448. doi: 10.1111/1756-185X.13392. Epub 2018 Oct 24.

Abstract

BACKGROUND

Anti-DNA/N-methyl-D-aspartate receptor 2 (NR2) antibodies (anti-DNA/NR2 antibodies) are a subset of anti-DNA autoantibodies that cross-react with the extracellular domain of the GluN2A/GluN2B subunits of NR2. These antibodies induce apoptosis of hippocampus neurons and psychiatric disorder in mice and humans. Neuropsychiatric system lupus erythematosus (NPSLE) can develop after initiation of corticosteroids (post-steroid neuropsychiatric manifestation: PSNP) or before treatment (de novo NPSLE); however, pathophysiological differences between these subtypes remain unclear. The objective of this study was to clarify the prevalence of anti-DNA/NR2 antibodies in patients with NPSLE.

METHODS

This study involved a cohort of patients with NPSLE admitted to our hospital. NPSLE patients were classified into two groups, de novo NPSLE and PSNP-SLE. Serum anti-DNA antibodies and anti-DNA/NR2 antibodies were measured by enzyme-linked immunosorbent assays.

RESULTS

Serum samples were obtained from 24 patients with de novo NPSLE, 25 with PSNP-SLE and 76 healthy controls (HC). The level of anti-DNA/NR2 antibodies in patients with de novo NPSLE and PSNP-SLE were also higher than those in HC. Positive correlation between anti-DNA antibodies and anti-DNA/NR2 antibodies were found in PSNP-SLE, but was not significant in de novo NPSLE.

CONCLUSION

The levels of anti-DNA/NR2 antibodies in PSNP-SLE were similar to those in de novo NPSLE. Anti-DNA/NR2 antibodies in PSNP-SLE were suggested as a dominant subset of anti-DNA antibodies, indicating that anti-DNA/NR2 antibodies may be a predictive factor in PSNP-SLE.

摘要

背景

抗DNA/N-甲基-D-天冬氨酸受体2(NR2)抗体(抗DNA/NR2抗体)是一类抗DNA自身抗体的亚群,可与NR2的GluN2A/GluN2B亚基的细胞外结构域发生交叉反应。这些抗体可诱导小鼠和人类海马神经元凋亡及精神障碍。神经精神系统红斑狼疮(NPSLE)可在使用皮质类固醇后发生(类固醇治疗后神经精神表现:PSNP)或在治疗前出现(新发NPSLE);然而,这些亚型之间的病理生理差异仍不清楚。本研究的目的是明确NPSLE患者中抗DNA/NR2抗体的患病率。

方法

本研究纳入了我院收治的一组NPSLE患者。NPSLE患者被分为两组,即新发NPSLE组和PSNP-SLE组。采用酶联免疫吸附测定法检测血清抗DNA抗体和抗DNA/NR2抗体。

结果

采集了24例新发NPSLE患者、25例PSNP-SLE患者和76例健康对照(HC)的血清样本。新发NPSLE患者和PSNP-SLE患者的抗DNA/NR2抗体水平也高于HC组。在PSNP-SLE组中发现抗DNA抗体与抗DNA/NR2抗体呈正相关,但在新发NPSLE组中不显著。

结论

PSNP-SLE组中抗DNA/NR2抗体水平与新发NPSLE组相似。PSNP-SLE组中的抗DNA/NR2抗体被认为是抗DNA抗体的主要亚群,表明抗DNA/NR2抗体可能是PSNP-SLE的一个预测因素。

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