关键词: ELISA GAD65 autoantibodies autoimmune encephalitis cell-based assay diabetes type 1 epilepsy immunohistochemistry neuronal autoantibodies

来  源:   DOI:10.3389/fneur.2023.1111063   PDF(Pubmed)

Abstract:
UNASSIGNED: Anti-GAD65 autoantibodies (GAD65-Abs) may occur in patients with epilepsy and other neurological disorders, but the clinical significance is not clear-cut. Whereas high levels of GAD65-Abs are considered pathogenic in neuropsychiatric disorders, low or moderate levels are only considered as mere bystanders in, e.g., diabetes mellitus type 1 (DM1). The value of cell-based assays (CBA) and immunohistochemistry (IHC) for GAD65-Abs detection has not been clearly evaluated in this context.
UNASSIGNED: To re-evaluate the assumption that high levels of GAD65-Abs are related to neuropsychiatric disorders and lower levels only to DM1 and to compare ELISA results with CBA and IHC to determine the additional value of these tests.
UNASSIGNED: 111 sera previously assessed for GAD65-Abs by ELISA in routine clinical practice were studied. Clinical indications for testing were, e.g., suspected autoimmune encephalitis or epilepsy (neuropsychiatric cohort; n = 71, 7 cases were initially tested positive for GAD65-Abs by ELISA), and DM1 or latent autoimmune diabetes in adults (DM1/LADA cohort (n = 40, all were initially tested positive)). Sera were re-tested for GAD65-Abs by ELISA, CBA, and IHC. Also, we examined the possible presence of GAD67-Abs by CBA and of other neuronal autoantibodies by IHC. Samples that showed IHC patterns different from GAD65 were further tested by selected CBAs.
UNASSIGNED: ELISA retested GAD65-Abs level in patients with neuropsychiatric diseases was higher than in patients with DM1/LADA (only retested positive samples were compared; 6 vs. 38; median 47,092 U/mL vs. 581 U/mL; p = 0.02). GAD-Abs showed positive both by CBA and IHC only if antibody levels were above 10,000 U/mL, without a difference in prevalence between the studied cohorts. We found other neuronal antibodies in one patient with epilepsy (mGluR1-Abs, GAD-Abs negative), and in a patient with encephalitis, and two patients with LADA.
UNASSIGNED: GAD65-Abs levels are significantly higher in patients with neuropsychiatric disease than in patients with DM1/LADA, however, positivity in CBA and IHC only correlates with high levels of GAD65-Abs, and not with the underlying diseases.
摘要:
抗GAD65自身抗体(GAD65-Abs)可能发生在癫痫和其他神经系统疾病的患者中,但临床意义尚不明确。尽管高水平的GAD65-Ab被认为在神经精神疾病中具有致病性,低或中等水平只被认为是纯粹的旁观者,例如,1型糖尿病(DM1)。在这种情况下,尚未明确评估基于细胞的测定(CBA)和免疫组织化学(IHC)对GAD65-Ab检测的价值。
为了重新评估高水平的GAD65-Ab与神经精神疾病有关而低水平仅与DM1有关的假设,并将ELISA结果与CBA和IHC进行比较以确定这些测试的附加价值。
研究了先前在常规临床实践中通过ELISA评估的GAD65-Ab的111份血清。测试的临床适应症是,例如,疑似自身免疫性脑炎或癫痫(神经精神队列;n=71,7例最初通过ELISA检测GAD65-Abs呈阳性),和DM1或成人隐匿性自身免疫性糖尿病(DM1/LADA队列(n=40,最初全部检测为阳性))。通过ELISA重新检测血清中的GAD65-Abs,CBA,IHC。此外,我们通过CBA检查了GAD67-Abs的可能存在,通过IHC检查了其他神经元自身抗体的可能存在.通过选择的CBA进一步测试显示不同于GAD65的IHC模式的样品。
ELISA重新测试神经精神疾病患者的GAD65-Abs水平高于DM1/LADA患者(仅比较了重新测试的阳性样品;6vs.38;中位数47,092U/mL与581U/mL;p=0.02)。只有当抗体水平高于10,000U/mL时,GAD-Ab通过CBA和IHC均显示阳性,研究队列之间的患病率没有差异。我们在一名癫痫患者中发现了其他神经元抗体(mGluR1-Abs,GAD-Abs阴性),在脑炎患者中,还有两名LADA患者.
神经精神疾病患者的GAD65-Abs水平明显高于DM1/LADA患者,然而,CBA和IHC阳性仅与高水平的GAD65-Abs相关,而不是潜在的疾病。
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