Early active multiple sclerosis (MS) lesions can be classified histologically into three main immunopathological patterns of demyelination (patterns I-III), which suggest pathogenic heterogeneity and may predict therapy response. Patterns I and II show signs of immune-mediated demyelination, but only pattern II is associated with antibody/complement deposition. In pattern III lesions, which include Baló's concentric sclerosis, primary oligodendrocyte damage was proposed. Serum antibody reactivities could reflect disease pathogenesis and thus distinguish histopathologically defined MS patterns. We established a customized microarray with more than 700 peptides that represent human and viral antigens potentially relevant for inflammatory demyelinating CNS diseases, and tested sera from 66 patients (pattern I n = 12; II n = 29; III n = 25, including 8 with Baló's), healthy controls, patients with Sjögren's syndrome and stroke patients. Cell-based assays were performed for aquaporin 1 (AQP1) and AQP4 antibody detection. No single peptide showed differential binding among study cohorts. Because antibodies can react with different peptides from one protein, we also analyzed groups of peptides. Patients with pattern II showed significantly higher reactivities to Nogo-A peptides as compared to patterns I (p = 0.02) and III (p = 0.02). Pattern III patients showed higher reactivities to AQP1 (compared to pattern I p = 0.002, pattern II p = 0.001) and varicella zoster virus (VZV, compared to pattern II p = 0.05). In patients with Baló's, AQP1 reactivity was also significantly higher compared to patients without Baló's (p = 0.04), and the former revealed distinct antibody signatures. Histologically, Baló's patients showed loss of AQP1 and AQP4 in demyelinating lesions, but no antibodies binding conformational AQP1 or AQP4 were detected. In summary, higher reactivities to Nogo-A peptides in pattern II patients could be relevant for enhanced axonal repair and remyelination. Higher reactivities to AQP1 peptides in pattern III patients and its subgroup of Baló's patients possibly reflect astrocytic damage. Finally, latent VZV infection may cause peripheral immune activation.

中文翻译：

---

具有组织病理学定义的多发性硬化模式患者的抗体特征。

早期活动性多发性硬化症（MS）病变可从组织学上分为脱髓鞘的三种主要免疫病理模式（模式I-III），提示病原性异质性并可以预测治疗反应。模式I和II显示了免疫介导的脱髓鞘的迹象，但只有模式II与抗体/补体沉积有关。在III型病变中，包括Baló's同心性硬化，提出了原发性少突胶质细胞损伤。血清抗体反应性可以反映疾病的发病机理，从而区分组织病理学定义的MS模式。我们建立了定制化的微阵列，其中包含700多种肽，它们代表与炎症性脱髓鞘中枢神经系统疾病潜在相关的人和病毒抗原，并测试了66位患者的血清（模式I n = 12； II n = 29； III n = 25，包括8例Baló's病，健康对照，干燥综合征患者和中风患者。对水通道蛋白1（AQP1）和AQP4抗体进行了基于细胞的检测。研究队列中没有单个肽显示出差异结合。由于抗体可以与一种蛋白质中的不同肽发生反应，因此我们还分析了各组肽。与模式I（p = 0.02）和模式III（p = 0.02）相比，具有模式II的患者对Nogo-A肽的反应性明显更高。III型患者显示出对AQP1（与Ip = 0.002，IIP = 0.001模式）和水痘带状疱疹病毒（VZV，相比于IIp = 0.05）具有更高的反应性。与没有Baló's的患者相比，患有Baló's的患者的AQP1反应性也显着更高（p = 0.04），前者显示出独特的抗体特征。组织学上，Baló的患者显示脱髓鞘性病变中AQP1和AQP4缺失，但未检测到结合构象AQP1或AQP4的抗体。总之，II型患者对Nogo-A肽的更高反应性可能与轴突修复和髓鞘再生增强有关。III型患者及其Baló患者亚组对AQP1肽的更高反应性可能反映了星形细胞损伤。最后，潜在的VZV感染可能导致外周免疫激活。II型患者对Nogo-A肽的更高反应性可能与增强轴突修复和髓鞘再生有关。III型患者及其Baló患者亚组对AQP1肽的更高反应性可能反映了星形细胞损伤。最后，潜在的VZV感染可能导致外周免疫激活。II型患者对Nogo-A肽的更高反应性可能与增强轴突修复和髓鞘再生有关。III型患者及其Baló患者亚组对AQP1肽的更高反应性可能反映了星形细胞损伤。最后，潜在的VZV感染可能导致外周免疫激活。