Antibody signatures in patients with histopathologically defined multiple sclerosis patterns

Stork, Lidia; Ellenberger, David; Ruprecht, Klemens; Reindl, Markus; Beissbarth, Tim; Friede, Tim; Kuempfel, Tania; Gerdes, Lisa A.; Gloth, Mareike; Liman, Thomas; Paul, Friedemann; Brueck, Wolfgang und Metz, Imke (2020): Antibody signatures in patients with histopathologically defined multiple sclerosis patterns. In: Acta Neuropathologica, Bd. 139, Nr. 3: S. 547-564

Abstract

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 Balo'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 Balo's), healthy controls, patients with Sjogren'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 Balo's, AQP1 reactivity was also significantly higher compared to patients without Balo's (p = 0.04), and the former revealed distinct antibody signatures. Histologically, Balo'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 Balo's patients possibly reflect astrocytic damage. Finally, latent VZV infection may cause peripheral immune activation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0001-6322
• Sprache: Englisch