From the Department of Neurology (L.A., J.M., K.S., D.H., A.-M.B., H.S., B.F., C.S., K.D.), University Hospital of Würzburg; Department of Neurology (I.A., K.P.), St. Josef Hospital Bochum, Ruhr University of Bochum, Germany; Department of Neurology (I.A.), I.M. Sechenov First Moscow State Medical University, Russia; Department of Neurology (F.B., C.D.), University Medical Center of the Johannes Gutenberg University, Mainz; Department of Neurology (J.D., S.M.), University Hospital Ulm; German Center for Neurodegenerative Diseases (DZNE) (J.D.), Ulm; Department of Neurologic Rehabilitation (F.D.), Asklepios Schloßberg-Klinik, Bad König; Department of Neurology (A.G.), Tübingen University Hospital; Hans Berger Department of Neurology (A.J.), Jena University Hospital; Neuroimmunology Section (F.L.), Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck; Department of Neurology (F.L.), Kiel University; Department of Neurology (M.M.), Klinikum Würzburg Mitte gGmbH, Standort Juliusspital; Department of Neurology (P.M.), LVR-Klinik, Bonn; Department of Pathology (M.R.), Julius Maximilian University of Würzburg; Department of Neurology (A.-D.S.), Sächsisches Krankenhaus Altscherbitz, Schkeuditz; Department of Neurology (M.W.), Bundeswehrkrankenhaus Ulm; and Department of Neurology (G.S.W.), KRH Klinikum Nordstadt, Hannover, Germany.
Neurol Neuroimmunol Neuroinflamm. 2022 Mar 21;9(3). doi: 10.1212/NXI.0000000000001163. Print 2022 May.
Nodo-paranodopathies are peripheral neuropathies with dysfunction of the node of Ranvier. Affected patients who are seropositive for antibodies against adhesion molecules like contactin-1 and neurofascin show distinct clinical features and a disruption of the paranodal complex. An axoglial dysjunction is also a characteristic finding of diabetic neuropathy. Here, we aim to investigate a possible association of antibody-mediated nodo-paranodopathy and diabetes mellitus (DM).
We retrospectively analyzed clinical data of 227 patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome from multiple centers in Germany who had undergone diagnostic testing for antiparanodal antibodies targeting neurofascin-155, pan-neurofascin, contactin-1-associated protein 1, and contactin-1. To study possible direct pathogenic effects of antiparanodal antibodies, we performed immunofluorescence binding assays on human pancreatic tissue sections.
The frequency of DM was 33.3% in seropositive patients and thus higher compared with seronegative patients (14.1%, OR = 3.04, 95% CI = 1.31-6.80). The relative risk of DM in seropositive patients was 3.4-fold higher compared with the general German population. Seropositive patients with DM most frequently harbored anti-contactin-1 antibodies and had higher antibody titers than seropositive patients without DM. The diagnosis of DM preceded the onset of neuropathy in seropositive patients. No immunoreactivity of antiparanodal antibodies against pancreatic tissue was detected.
We report an association of nodo-paranodopathy and DM. Our results suggest that DM may be a potential risk factor for predisposing to developing nodo-paranodopathy and argue against DM being induced by the autoantibodies. Our findings set the basis for further research investigating underlying immunopathogenetic connections.
结节性-神经节周神经病是一种伴有郎飞结功能障碍的周围神经病。伴有针对黏附分子（如接触蛋白-1 和神经束蛋白）抗体的血清阳性患者具有独特的临床特征和节周复合物破坏。轴索-胶质分离也是糖尿病性神经病的特征性发现。在这里，我们旨在研究抗体介导的结节性-神经节周神经病与糖尿病（DM）之间可能存在的关联。
我们回顾性分析了来自德国多个中心的 227 例慢性炎症性脱髓鞘性多发性神经根神经病和格林-巴利综合征患者的临床数据，这些患者曾接受过针对神经束蛋白-155、神经束蛋白-1、接触蛋白-1 相关蛋白 1 和接触蛋白-1 的抗节周抗体的诊断检测。为了研究抗节周抗体可能存在的直接致病作用，我们在人胰腺组织切片上进行了免疫荧光结合分析。
在血清阳性患者中，DM 的频率为 33.3%，高于血清阴性患者（14.1%，OR=3.04，95%CI=1.31-6.80）。与一般德国人群相比，血清阳性患者发生 DM 的相对风险高 3.4 倍。血清阳性且合并 DM 的患者最常携带抗接触蛋白-1 抗体，且抗体滴度高于不合并 DM 的血清阳性患者。在血清阳性患者中，DM 的诊断先于神经病的发病。未检测到抗节周抗体对胰腺组织的免疫反应性。
我们报告了结节性-神经节周神经病与 DM 之间存在关联。我们的结果表明，DM 可能是导致发生结节性-神经节周神经病的潜在危险因素，但不能证明 DM 是由自身抗体引起的。我们的研究结果为进一步研究潜在的免疫发病机制联系奠定了基础。
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