本研究意在检测非神经性自身免疫疾病中是否存在针对神经表面抗原的自身抗体，提示更广泛的耐受性丧失。患者和匹配的健康对照(HD)血清来自四类人群：1)类风湿关节炎(RA)(n = 194，HD n = 64)，2)1型 (T1D)(n = 200，HD n = 200)，3)系统性红斑狼疮(SLE)(n = 200，HD n = 67;神经-SLE n = 49，HD n = 33)，及4)神经自身免疫的对照组(复发-缓解多发性硬化[ MS] n = 110，HD n = 110;原发性进展型MS n = 9;继发性进展型MS n = 10;视神经脊髓炎谱系障碍n = 15;和其他神经系统疾病n = 26)。应用流式细胞术，使用基于活细胞免疫荧光测定法筛选1287个特殊血清样本中四种神经表面抗原(髓鞘少突胶质细胞糖蛋白、水通道蛋白4、乙酰胆碱受体和肌肉特异性激酶)。通过倍比稀释或放射免疫测定通过自身抗体滴度定量进一步验证筛选的阳性样本。在RA和T1D患者中未检测到针对神经表面抗原的自身抗体，而少数SLE患者(2 / 200,1%)携带此类自身抗体。正如预期的结果一样，在中枢神经系统自身免疫对照组中，针对水通道蛋白4的自身抗体和针对髓鞘少突胶质细胞糖蛋白的高滴度抗体对视神经脊髓炎谱系疾病具有特异性。本研究得出结论：神经自身抗体不会跨越RA和T1D的疾病屏障。SLE中神经自身抗体的轻度增加可能与这种系统性自身免疫疾病中B细胞耐受性的更广泛丧失相关。

附原文：Abstract The aim of this studywas to test whether autoantibodies against neurologic surface Ags are found innonneurologic autoimmune diseases, indicating a broader loss of tolerance.Patient and matchedhealthy donor (HD) sera were derived from four large cohorts: 1)rheumatoid arthritis(RA) (n= 194,HDn= 64), 2) type 1 diabetes (T1D) (n= 200,HDn= 200), 3) systemic lupus erythematosus (SLE) (n=200, HDn= 67; neuro-SLEn= 49, HDn=33), and 4) a control cohort of neurologic autoimmunity (relapsing-remittingmultiple sclerosis [MS]n= 110, HDn= 110;primary progressive MSn= 9; secondary progressive MSn=10; neuromyelitis optica spectrum disordersn= 15; and otherneurologic disordersn= 26). Screening of 1287 unique serumsamples against four neurologic surface Ags (myelin oligodendrocyteglycoprotein, aquaporin 4, acetylcholine receptor, and muscle-specific kinase)was performed with live cell-based immunofluorescence assays using flowcytometry. Positive samples identified in the screening were further validatedusing autoantibody titer quantification by serial dilutions orradioimmunoassay. Autoantibodies against neurologic surface Ags were notobserved in RA and T1D patients, whereas SLE patients harbored suchautoantibodies in rare cases (2/200, 1%). Within the CNS autoimmunity controlcohort, autoantibodies against aquaporin 4 and high-titer Abs against myelinoligodendrocyte glycoprotein were, as expected, specific for neuromyelitisoptica spectrum disorders. We conclude that neurologic autoantibodies do notcross disease barriers in RA and T1D. The finding of mildly increasedneurologic autoantibodies in SLE may be consistent with a broader loss of Bcell tolerance in this form of systemic autoimmunity.

引自：Stathopoulos P,Chastre A,Waters P, et al. Autoantibodies against Neurologic Antigens inNonneurologic Autoimmunity.J Immunol.2019Mar 1. pii: ji1801295. doi: 10.4049/jimmunol.1801295. [Epub ahead of print]