The Feinstein Institute for Medical Research, Manhasset, New York.
Kitasato University School of Medicine, Kanagawa, Japan.
Arthritis Rheumatol. 2018 Feb;70(2):277-286. doi: 10.1002/art.40356. Epub 2018 Jan 9.
IgG anti-DWEYS antibodies cross-reactive with DNA and the N-methyl-d-aspartate receptor subunits GluN2A and GluN2B are known to be associated with neuropsychiatric systemic lupus erythematosus (NPSLE). IgG anti-DWEYS have not been investigated in demyelinating NPSLE or in another demyelinating disorder, neuromyelitis optica spectrum disorder (NMOSD), which is a disease also found mainly in young women and associated with aquaporin 4 (AQP-4) or myelin oligodendrocyte glycoprotein (MOG) antibodies. This study was undertaken to investigate the frequency of all of these brain-reactive antibodies in patients with NPSLE, those with demyelinating NPSLE, and those with NMOSD.
Serum samples from patients with NPSLE (n = 108), patients with SLE without neuropsychiatric manifestations (n = 38), patients with NMOSD (n = 33), and healthy controls (n = 106) were assessed for the frequency of IgG anti-brain antibodies as well as IgG antibodies to AQP-4, MOG, GluN2A/GluN2B, and double-stranded DNA (dsDNA).
Sera were positive for IgG anti-AQP-4 antibodies in 27 (82%) of 33 patients with NMOSD and 3 (27%) of 11 patients with demyelinating NPSLE, whereas all sera from patients with non-demyelinating NPSLE, patients with SLE, and healthy controls were negative for IgG anti-AQP-4. IgG anti-MOG were detected at high titers in 3 (50%) of 6 patients with NMOSD who were negative for IgG anti-AQP-4, and at low titers in 2 (18%) of 11 patients with demyelinating NPSLE and 1 (1%) of 97 patients with non-demyelinating NPSLE. IgG antibodies to dsDNA were present in 11 (33%) of 33 patients with NMOSD. Only 4 (12%) of 33 patients with NMOSD were positive for IgG anti-DWEYS, compared to 11 (29%) of 38 patients with SLE and 59 (55%) of 108 patients with NPSLE. IgG anti-DWEYS antibodies were present in 56 (58%) of 97 patients with non-demyelinating NPSLE and 3 (27%) of 11 patients with demyelinating NPSLE. Serum IgG brain-reactive antibodies were present at a similar frequency in patients with non-demyelinating NPSLE (72 [75%] of 96), those with demyelinating NPSLE (9 [82%] of 11), and those with SLE (32 [84%] of 38), but were less frequent in patients with NMOSD (20 [61%] of 33).
Patients with demyelinating NPSLE should be tested for IgG antibodies to AQP-4, MOG, and DWEYS. IgG anti-AQP-4 can be considered diagnostic for NMOSD, whereas none of these antibodies appear to be diagnostic for demyelinating NPSLE. Moreover, IgG anti-dsDNA are present in patients with NMOSD but are not cross-reactive with IgG anti-DWEYS, indicating that the antigenic stimulus and mechanisms of tissue damage are potentially different between demyelinating NPSLE and NMOSD.
与 DNA 以及 N-甲基-D-天冬氨酸受体亚基 GluN2A 和 GluN2B 发生交叉反应的 IgG 抗-DWEYS 抗体已知与神经精神性系统性红斑狼疮（NPSLE）相关。尚未在脱髓鞘性 NPSLE 或另一种脱髓鞘性疾病视神经脊髓炎谱系障碍（NMOSD）中研究 IgG 抗-DWEYS，NMOSD 主要发生在年轻女性中，与水通道蛋白 4（AQP-4）或髓鞘少突胶质细胞糖蛋白（MOG）抗体相关。本研究旨在调查这些脑反应性抗体在 NPSLE 患者、脱髓鞘性 NPSLE 患者和 NMOSD 患者中的频率。
评估 108 例 NPSLE 患者（n = 108）、38 例无神经精神表现的系统性红斑狼疮患者（n = 38）、33 例 NMOSD 患者（n = 33）和 106 例健康对照者（n = 106）血清样本中 IgG 抗脑抗体以及 IgG 抗体对 AQP-4、MOG、GluN2A/GluN2B 和双链 DNA（dsDNA）的频率。
33 例 NMOSD 患者中有 27 例（82%）和 11 例脱髓鞘性 NPSLE 患者中的 3 例（27%）血清 IgG 抗-AQP-4 抗体阳性，而所有非脱髓鞘性 NPSLE 患者、系统性红斑狼疮患者和健康对照者的血清 IgG 抗-AQP-4 均为阴性。6 例 NMOSD 患者 IgG 抗-MOG 抗体高滴度阳性，其中 3 例（50%）IgG 抗-AQP-4 抗体阴性，11 例脱髓鞘性 NPSLE 患者中有 2 例（18%）和 97 例非脱髓鞘性 NPSLE 患者中有 1 例（1%）低滴度阳性。11 例 NMOSD 患者（33%）血清 IgG 抗体 dsDNA 阳性。与 38 例系统性红斑狼疮患者中的 11 例（29%）和 96 例非脱髓鞘性 NPSLE 患者中的 56 例（58%）相比，NMOSD 患者中只有 4 例（12%）为 IgG 抗-DWEYS 阳性，11 例脱髓鞘性 NPSLE 患者中有 3 例（27%）阳性。56 例非脱髓鞘性 NPSLE 患者（58%）和 11 例脱髓鞘性 NPSLE 患者中有 3 例（27%）血清 IgG 脑反应性抗体阳性。非脱髓鞘性 NPSLE 患者（72 [75%] 例 96）、脱髓鞘性 NPSLE 患者（9 [82%] 例 11）和系统性红斑狼疮患者（32 [84%] 例 38）的血清 IgG 脑反应性抗体阳性频率相似，但 NMOSD 患者的阳性频率较低（33 例中有 20 例 [61%]）。
脱髓鞘性 NPSLE 患者应检测 IgG 抗体对 AQP-4、MOG 和 DWEYS。IgG 抗-AQP-4 可作为 NMOSD 的诊断指标，而这些抗体均不能作为脱髓鞘性 NPSLE 的诊断指标。此外，NMOSD 患者中存在 IgG 抗-dsDNA，但与 IgG 抗-DWEYS 无交叉反应，表明脱髓鞘性 NPSLE 和 NMOSD 之间潜在的抗原刺激和组织损伤机制可能不同。
