Autoantibodies against Neurologic Antigens in Nonneurologic Autoimmunity
Autoantibodies against Neurologic Antigens in Nonneurologic Autoimmunity
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DOI：
10.4049/jimmunol.1801295
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发表时间：
2019-04-15
影响因子：
4.4
通讯作者：
O'Connor, Kevin C.
中科院分区：
文献类型：
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作者：
Stathopoulos, Panos;Chastre, Anne;O'Connor, Kevin C.
本研究的目的是测试是否在非神经系统自身免疫性疾病中发现针对神经系统表面抗原的自身抗体，表明更广泛的耐受性丧失。患者和匹配的健康供体（HD）血清来源于四个大的群组：1）类风湿性关节炎（RA）（n = 194，HD n = 64），2）1型糖尿病（T1 D）（n = 200，HD n = 200），3）系统性红斑狼疮（SLE）（n = 200，HD n = 67;神经系统性SLE n = 49，HD n = 33），和4）神经系统自身免疫的对照队列（复发缓解型多发性硬化[MS] n = 110，HD n = 110;原发性进展型MS n = 9;继发性进展型MS n = 10;视神经肌萎缩性疾病n = 15;其他神经系统疾病n = 26）。筛选1287个独特的血清样本对四个神经系统的表面抗原（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）进行活细胞为基础的免疫荧光分析，使用流式细胞术。通过连续稀释或放射免疫测定，使用自身抗体滴度定量进一步验证筛选中鉴别的阳性样本。在RA和T1 D患者中未观察到针对神经系统表面抗原的自身抗体，而SLE患者在罕见病例中携带此类自身抗体（2/200，1%）。在中枢神经系统自身免疫对照队列中，正如预期的那样，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。我们的结论是，神经系统自身抗体不跨越疾病的障碍，类风湿关节炎和T1 D。SLE中神经系统自身抗体轻度增加的发现可能与这种形式的系统性自身免疫中B细胞耐受性的广泛丧失一致。
The aim of this study was to test whether autoantibodies against neurologic surface Ags are found in nonneurologic autoimmune diseases, indicating a broader loss of tolerance. Patient and matched healthy donor (HD) sera were derived from four large cohorts: 1) rheumatoid arthritis (RA) (n = 194, HD n = 64), 2) type 1 diabetes (T1D) (n = 200, HD n = 200), 3) systemic lupus erythematosus (SLE) (n = 200, HD n = 67; neuro-SLE n = 49, HD n = 33), and 4) a control cohort of neurologic autoimmunity (relapsing-remitting multiple sclerosis [MS] n = 110, HD n = 110; primary progressive MS n = 9; secondary progressive MS n = 10; neuromyelitis optica spectrum disorders n = 15; and other neurologic disorders n = 26). Screening of 1287 unique serum samples against four neurologic surface Ags (myelin oligodendrocyte glycoprotein, aquaporin 4, acetylcholine receptor, and muscle-specific kinase) was performed with live cell-based immunofluorescence assays using flow cytometry. Positive samples identified in the screening were further validated using autoantibody titer quantification by serial dilutions or radioimmunoassay. Autoantibodies against neurologic surface Ags were not observed in RA and T1D patients, whereas SLE patients harbored such autoantibodies in rare cases (2/200, 1%). Within the CNS autoimmunity control cohort, autoantibodies against aquaporin 4 and high-titer Abs against myelin oligodendrocyte glycoprotein were, as expected, specific for neuromyelitis optica spectrum disorders. We conclude that neurologic autoantibodies do not cross disease barriers in RA and T1D. The finding of mildly increased neurologic autoantibodies in SLE may be consistent with a broader loss of B cell tolerance in this form of systemic autoimmunity.