From the Department of Neurology (S.R., S.S., B.H., L.A., C. Sommer, K.D.); Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine Centre for Interdisciplinary Pain Medicine (B.H.); Institute of Experimental Biomedicine (R.A., A.Z.), University Hospital Würzburg; German Center for Neurodegenerative Diseases (DZNE) Berlin (F.A.A., H.P.); Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität Berlin; Section Translational Neuroimmunology (D.B., C.G.), Department of Neurology, Jena University Hospital; Department of Neurology (C.D.), University Medical Center of the Johannes Gutenberg University, Mainz; Department of Neurology (J.D., Z.E.), University Hospital Ulm; Department of Neurology (T.H., H.T.), Therapiezentrum Burgau; Department of Neurology (S.K.), Friedrich Baur Institute, LMU University Hospital, LMU Munich; Department of Neurology (M. Marziniak), Kbo-Isar-Amper-Hospital Munich East; Department of Neurology (M. Mäurer), Klinikum Würzburg Mitte gGmbH, Standort Juliusspital; Department of Neurology (F.S.), LMU University Hospital, LMU, Munich; Department of Neurology (B.S.), DKD HELIOS Klinik Wiesbaden; Department of Paediatric and Adolescent Medicine (C. Steen), St Joseph Hospital, Berlin; Department of Neurology (A.T.), HELIOS Klinikum Erfurt; and Neurologische Praxis Dres. Wessely (L.W.), Menden, Germany.
Neurol Neuroimmunol Neuroinflamm. 2024 Sep;11(5):e200295. doi: 10.1212/NXI.0000000000200295. Epub 2024 Aug 22.
Autoimmune nodopathies with antibodies against the paranodal proteins show a distinct phenotype of a severe sensorimotor neuropathy. In some patients, complete remission can be achieved after treatment with rituximab whereas others show a chronic course. For optimal planning of treatment, predicting the course of disease and therapeutic response is crucial.
We stimulated peripheral blood mononuclear cells in vitro to find out whether secretion of specific autoantibodies may be a predictor of the course of disease and response to rituximab.
Three patterns could be identified: In most patients with anti-Neurofascin-155-, anti-Contactin-1-, and anti-Caspr1-IgG4 autoantibodies, in vitro production of autoantibodies was detected, indicating autoantigen-specific memory B cells and short-lived plasma cells/plasmablasts as the major source of autoantibodies. These patients generally showed a good response to rituximab. In a subgroup of patients with anti-Neurofascin-155-IgG4 autoantibodies and insufficient response to rituximab, no in vitro autoantibody production was found despite high serum titers, indicating autoantibody secretion by long-lived plasma cells outside the peripheral blood. In the patients with anti-pan-Neurofascin autoantibodies-all with a monophasic course of disease-no in vitro autoantibody production could be measured, suggesting a lack of autoantigen-specific memory B cells. In some of them, autoantibody production by unstimulated cells was detectable, presumably corresponding to high amounts of autoantigen-specific plasmablasts-well in line with a severe but monophasic course of disease.
Our data suggest that different B-cell responses may occur in autoimmune nodopathies and may serve as markers of courses of disease and response to rituximab.
针对连接蛋白蛋白的自身抗体阳性的自身免疫性神经节病表现为严重的感觉运动神经病的特殊表型。在一些患者中，利妥昔单抗治疗后可达到完全缓解，而另一些患者则表现为慢性病程。为了优化治疗方案，预测疾病过程和治疗反应至关重要。
我们在体外刺激外周血单核细胞，以确定特异性自身抗体的分泌是否可作为疾病过程和利妥昔单抗反应的预测指标。
可识别出三种模式：在大多数抗神经束蛋白 155、抗接触蛋白 1 和抗 Caspr1-IgG4 自身抗体阳性的患者中，检测到体外产生自身抗体，表明自身抗原特异性记忆 B 细胞和短暂存活的浆细胞/浆母细胞是自身抗体的主要来源。这些患者通常对利妥昔单抗反应良好。在一小部分抗神经束蛋白 155-IgG4 自身抗体阳性且对利妥昔单抗反应不足的患者中，尽管血清滴度较高，但未发现体外自身抗体产生，表明外周血外的长寿浆细胞分泌自身抗体。在具有单相病程的所有抗泛神经束蛋白自身抗体阳性患者中，无法测量到体外自身抗体产生，表明缺乏自身抗原特异性记忆 B 细胞。在其中一些患者中，可检测到未受刺激细胞的自身抗体产生，可能对应于大量的自身抗原特异性浆母细胞，与严重但单相病程相符。
我们的数据表明，自身免疫性神经节病中可能发生不同的 B 细胞反应，并可作为疾病过程和利妥昔单抗反应的标志物。
