Central nervous system-specific antinuclear antibodies in patients with multiple sclerosis

J Neurol Sci. 2020 Feb 15:409:116619. doi: 10.1016/j.jns.2019.116619. Epub 2019 Dec 6.

Abstract

Background: Nuclear antigen released from central nervous system (CNS) cells undergoing destruction may induce production of antinuclear antibodies (ANA). We characterized the CNS-specific production of ANA in multiple sclerosis (MS).

Methods: We assessed CNS-ANA binding to mouse cerebellar cell nuclei by immunofluorescence assay (IFA) with sera from 104 MS patients (91 relapsing-remitting; 13 secondary progressive), 30 patients with neuromyelitis optica spectrum disorders (NMOSD), and 30 healthy controls (HCs). Conventional ANA (cANA) was detected by IFA using human epithelial type-2 cells. CNS-ANA-positive cANA-negative patients were termed CNS-specific ANA-positive. Western blotting (WB) was performed using mouse cerebellar nuclear fractions.

Results: CNS-specific ANA were more frequent in MS than in NMOSD patients or HCs (13.5% vs 0% for both comparisons, both p < .05) and were associated with HLA-DRB1*15:01 (p = .0174). WB revealed a common 55 kDa band in seven MS patients. Compared with CNS-specific ANA-negative MS patients, those with 55 kDa band-immunoreactive CNS-specific ANA showed a higher frequency of secondary progressive MS (42.9% vs 10.0%, p = .0387) and greater Expanded Disability Status Scale scores (4.50 ± 2.02 vs 2.92 ± 2.27, p = .0506).

Conclusions: The CNS-specific ANA was more frequently detected in MS patients than NMOSD patients or HCs. 55 kDa band-reactive CNS-specific ANA may reflect clinical disease progression in MS.

Keywords: Antinuclear antibodies; Central nervous system; Multiple sclerosis; Progression.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies, Antinuclear / blood*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / diagnostic imaging
  • Multiple Sclerosis, Chronic Progressive / blood*
  • Multiple Sclerosis, Chronic Progressive / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / blood*
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Neuromyelitis Optica / blood*
  • Neuromyelitis Optica / diagnostic imaging
  • Retrospective Studies

Substances

  • Antibodies, Antinuclear