Our study objective was testing for anti-neuronal autoantibodies within commercially available intravenous immunoglobulin (IVIg) preparations. Sixteen samples from 5 different commercially available IVIg preparations were tested with cell-based assays (CBA) and enzyme-linked immunosorbent assay (ELISA) to detect and characterize common neuronal autoantibodies, and with immunohistochemistry on teased fibers from mouse sciatic nerve and on mouse brain sections to screen for nodal and not yet identified neuronal antigens. In 15/16 IVIg preparations, anti-GAD antibodies were detected in titers ranging from 40 to 1507 IU/mL, as typically seen in type 1 diabetes, but not in the range (> 2000 IU/mL) seen in GAD-positive neurological patients. None of the preparations was however positive with anti-GAD CBA. Antibodies to AQP4 were also detected by ELISA in 15/16 IVIg preparations with titers comparable to those seen in AQP4-seropositive NMO patients; with CBA, however, all IVIg samples were AQP4-negative. IVIg preparations contained IgG-anti-MAG antibodies by ELISA at statistically significant higher titers compared to controls. Two of the 16 IVIg samples were positive for human 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies. All IVIg preparations were negative for antibodies to MOG, NMDAR, anti-nodal, and other neuronal-specific proteins. IVIg preparations contain antibodies against GAD and AQP4 in titers comparable to those seen in autoimmune patients when tested by ELISA, but not by CBA or tissue immunohistochemistry, suggesting that the autoantibodies within the IVIg are against linear rather than structural epitopes, as part of the natural antibody immune repertoire. The information is clinically important for diagnosis when testing patients’ sera after they have received therapy with IVIg to avoid false interpretation.

中文翻译：

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IVIg 制剂中的抗神经元抗体：在临床实践中的重要性。

我们的研究目标是测试市售静脉内免疫球蛋白 (IVIg) 制剂中的抗神经元自身抗体。使用基于细胞的测定法 (CBA) 和酶联免疫吸附测定法 (ELISA) 对来自 5 种不同的市售 IVIg 制剂的 16 个样品进行了测试，以检测和表征常见的神经元自身抗体，并在小鼠坐骨神经和小鼠大脑的挑逗纤维上进行免疫组织化学检测部分筛选淋巴结和尚未确定的神经元抗原。在 15/16 IVIg 制剂中，检测到抗 GAD 抗体的滴度范围为 40 至 1507 IU/mL，这在 1 型糖尿病中很常见，但在 GAD 阳性神经病学中的滴度范围内（> 2000 IU/mL）不耐心。然而，没有一种制剂对抗 GAD CBA 呈阳性。在 15/16 IVIg 制剂中也通过 ELISA 检测到 AQP4 抗体，其滴度与在 AQP4 血清阳性 NMO 患者中观察到的滴度相当；然而，对于 CBA，所有 IVIg 样本均为 AQP4 阴性。与对照相比，IVIg 制剂通过 ELISA 含有具有统计学显着更高滴度的 IgG-抗 MAG 抗体。16 个 IVIg 样本中有两个对人 3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMGCR) 抗体呈阳性。所有 IVIg 制剂对 MOG、NMDAR、抗结节和其他神经元特异性蛋白的抗体均为阴性。IVIg 制剂含有抗 GAD 和 AQP4 的抗体，其滴度与通过 ELISA 测试时在自身免疫患者中观察到的抗体相当，但通过 CBA 或组织免疫组织化学测试时却没有，这表明 IVIg 内的自身抗体是针对线性而不是结构表位的，作为天然抗体免疫库的一部分。在患者接受 IVIg 治疗后检测患者血清以避免错误解释时，该信息在临床上对诊断很重要。