抗 AGO1 抗体鉴定出一组自身免疫性感觉神经元病。
Anti-AGO1 Antibodies Identify a Subset of Autoimmune Sensory Neuronopathy.
机构信息
From the Department of Neurology (C.P.M., P.-B.V., K.F., J.-P.C., J.-C.G.A.), University Hospital of Saint-Etienne; Synaptopathies and Autoantibodies (SynatAc) Team (C.P.M., Y.T., L.-D.D., S.M.-C., V.R., K.F., C.L.M., J.H., J.-P.C., J.-C.G.A.), Institut NeuroMyoGène, MELIS, INSERM U1314/CNRS UMR 5284, Université Claude Bernard Lyon 1; Faculty of Medicine (C.P.M., Y.T., J.-P.C., J.-C.G.A.), University Jean Monnet, Saint-Étienne, Saint-Priest-en-Jarez; Department of Biochemistry (Y.T., C.L.M.), University Hospital of Saint-Etienne; French Reference Center on Paraneoplastic Neurological Syndrome (L.-D.D., S.M.-C., V.R., J.H., J.-P.C., J.-C.G.A.), Hospices Civils de Lyon, Hôpital Neurologique, Bron; Department of Internal Medicine (M.K.), University Hospital of Saint-Etienne; CIRI-Centre International de Recherche en Infectiologie (M.K., S.P.), Team GIMAP (Saint-Etienne), Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, UJM; CIC Inserm 1408 Vaccinology (M.K., S.P.), Saint-Etienne; Department of Immunology (S.P.), University Hospital of Saint-Etienne; and European Reference Center for Rare Neuromuscular Diseases (J.-P.C., J.-C.G.A.), Saint-Etienne Cedex 02, France.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2023 Apr 18;10(3). doi: 10.1212/NXI.0000000000200105. Print 2023 May.
BACKGROUND AND OBJECTIVES
Autoantibodies (Abs) improve diagnosis and treatment decisions of idiopathic neurologic disorders. Recently, we identified Abs against Argonaute (AGO) proteins as potential autoimmunity biomarkers in neurologic disorders. In this study, we aim to reveal (1) the frequency of AGO1 Abs in sensory neuronopathy (SNN), (2) titers and IgG subclasses, and (3) their clinical pattern including response to treatment.
METHODS
This retrospective multicentric case/control study screened 132 patients with SNN, 301 with non-SNN neuropathies, 274 with autoimmune diseases (AIDs), and 116 healthy controls (HCs) for AGO1 Abs through ELISA. Seropositive cases were also tested for IgG subclasses, titers, and conformation specificity.
RESULTS
AGO1 Abs occurred in 44 patients, comprising significantly more of those with SNN (17/132 [12.9%]) than those with non-SNN neuropathies (11/301 [3.7%]; = 0.001), those with AIDs (16/274 [5.8%]; = 0.02), or HCs (0/116; < 0.0001). Ab titers ranged from 1:100 to 1:100,000. IgG subclass was mainly IgG1, and 11/17 AGO1 Ab-positive SNN (65%) had a conformational epitope. AGO1 Ab-positive SNN was more severe than AGO1 Ab-negative SNN (e.g., SNN score: 12.2 vs 11.0, = 0.004), and they more frequently and more efficiently responded to immunomodulatory treatments than AGO1 Ab-negative SNN (7/13 [54%] vs 6/37 [16%], = 0.02). Regarding the type of treatments more precisely, this significant difference was confirmed for the use of IV immunoglobulins (IVIg) but not for steroids or second-line treatments. Multivariate logistic regression adjusted for potential confounders showed that AGO1 Ab positivity was the only predictor of response to treatment (OR 4.93, 1.10-22.24 95% CI, = 0.03).
DISCUSSION
Although AGO Abs are not specific for SNN, based on our retrospective data, they may identify a subset of cases with SNN with more severe features and a possibly better response to IVIg. The significance of AGO1 Abs in clinical practice needs to be explored on a larger series.
背景与目的
自身抗体（Abs）可改善特发性神经疾病的诊断和治疗决策。最近，我们发现 Argonaute（AGO）蛋白抗体可能是神经疾病中的潜在自身免疫生物标志物。在这项研究中，我们旨在揭示：（1）AGO1 抗体在感觉神经元病（SNN）中的频率；（2）滴度和 IgG 亚类；（3）它们的临床模式，包括对治疗的反应。
方法
这项回顾性多中心病例/对照研究通过 ELISA 筛查了 132 例 SNN 患者、301 例非 SNN 神经病变患者、274 例自身免疫性疾病（AIDs）患者和 116 例健康对照者的 AGO1 Abs。对血清阳性病例还进行了 IgG 亚类、滴度和构象特异性检测。
结果
AGO1 抗体出现在 44 例患者中，其中 SNN 患者明显多于非 SNN 神经病变患者（17/132 [12.9%] 比 11/301 [3.7%]； = 0.001）、AIDs 患者（16/274 [5.8%]； = 0.02）或健康对照者（0/116； < 0.0001）。抗体滴度范围为 1:100 至 1:100,000。IgG 亚类主要为 IgG1，17 例 AGO1 抗体阳性的 SNN 中有 11 例（65%）具有构象表位。AGO1 抗体阳性的 SNN 比 AGO1 抗体阴性的 SNN 更严重（例如，SNN 评分：12.2 比 11.0； = 0.004），且它们对免疫调节治疗的反应更频繁且更有效，比 AGO1 抗体阴性的 SNN 更有效（7/13 [54%] 比 6/37 [16%]； = 0.02）。更精确地针对治疗类型，这一显著差异在 IV 免疫球蛋白（IVIg）的使用中得到了确认，但在类固醇或二线治疗中没有得到确认。调整潜在混杂因素的多变量逻辑回归显示，AGO1 抗体阳性是治疗反应的唯一预测因素（OR 4.93，1.10-22.24 95%CI， = 0.03）。
讨论
尽管 AGO Abs 不是 SNN 的特异性抗体，但根据我们的回顾性数据，它们可能可以识别出具有更严重特征且可能对 IVIg 反应更好的 SNN 病例亚群。AGO1 Abs 在临床实践中的意义需要在更大的系列中进行探讨。
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