Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA.
Lupus Sci Med. 2021 Mar;8(1). doi: 10.1136/lupus-2020-000462.
SLE is a chronic multisystem autoimmune inflammatory disease impacting a number of organs, including the central nervous system (CNS). The pathophysiology of CNS lupus is multifactorial, making diagnosis problematic. Neurocognitive (NC) testing and specific biomarkers to identify the development of neuropsychiatric (NP) symptoms in lupus are needed. Paediatric patients with SLE have high incidence of NP disease . While serum anti-N-methyl-D-aspartate receptor (NMDAR) antibodies have shown promise as a biomarker of NP in adults with SLE, much less is known with regard to paediatric patients with SLE.
We performed a cross-sectional study in paediatric patients with SLE. Serum NMDAR antibodies were measured and compared with levels in patients with juvenile idiopathic arthritis (JIA). Formal NC testing was performed in accordance with the Childhood Arthritis & Rheumatology Research Alliance neuropsychological core test battery. NC functioning was compared in the two groups and with NMDAR antibody levels.
Serum NMDAR antibody levels were significantly higher in paediatric patients with SLE compared with patients with JIA. There were no significant correlations between NMDAR antibody levels and any measure of NC functioning. In an exploratory examination of anti-ribosomal P (RibP) antibody and NC functioning in a subset of patients with SLE, RibP antibody-positive patients exhibited worse scores for Verbal Memory Index and Design Fluency Test Switching compared with RibP antibody-negative patients. A globally significant association between disease status and NC functioning was observed. Specifically, patients with SLE had lower scores compared with patients with JIA for full-scale IQ, letter-word recognition, reading fluency and calculation skills after adjusting for multiple comparisons.
These collective results suggest that although serum NMDAR may serve as a biomarker, formal NC testing is superior in identifying paediatric patients with SLE with NP manifestations. RibP also may potentially serve as a biomarker of NP manifestations in paediatric patients with SLE. Additional and longitudinal studies are needed.
系统性红斑狼疮（SLE）是一种慢性多系统自身免疫性炎症性疾病，可影响包括中枢神经系统（CNS）在内的多个器官。中枢狼疮的病理生理学是多因素的，这使得诊断变得复杂。需要神经认知（NC）测试和特定的生物标志物来识别狼疮患者神经精神（NP）症状的发展。SLE 患儿 NP 疾病的发病率很高。虽然血清抗 N-甲基-D-天冬氨酸受体（NMDAR）抗体已被证明是成人 SLE 患者 NP 的生物标志物，但对于 SLE 患儿，人们对其了解甚少。
我们对 SLE 患儿进行了横断面研究。测量了血清 NMDAR 抗体，并与幼年特发性关节炎（JIA）患者进行了比较。按照儿童关节炎和风湿病研究联盟神经心理学核心测试组合进行了正式的 NC 测试。比较了两组之间的 NC 功能，并与 NMDAR 抗体水平进行了比较。
SLE 患儿血清 NMDAR 抗体水平明显高于 JIA 患儿。NMDAR 抗体水平与任何 NC 功能测量均无显著相关性。在 SLE 患者亚组的抗核糖体 P（RibP）抗体和 NC 功能的探索性检查中，与 RibP 抗体阴性患者相比，RibP 抗体阳性患者的言语记忆指数和设计流畅性测试转换的得分更差。疾病状态与 NC 功能之间存在显著的全局相关性。具体而言，调整了多次比较后，SLE 患者的全量表智商、字母词识别、阅读流畅性和计算技能得分均低于 JIA 患者。
这些综合结果表明，尽管血清 NMDAR 可能作为生物标志物，但正式的 NC 测试更能识别出有 NP 表现的 SLE 患儿。RibP 也可能是 SLE 患儿 NP 表现的潜在生物标志物。需要进一步和纵向研究。
