Toll-Like Receptor Homolog CD180 Expression Is Diminished on Natural Autoantibody-Producing B Cells of Patients with Autoimmune CNS Disorders

J Immunol Res. 2021 May 25:2021:9953317. doi: 10.1155/2021/9953317. eCollection 2021.

Abstract

Purpose: Decreased expression of TLR homolog CD180 in peripheral blood B cells and its potential role in antibody production have been described in autoimmune diseases. Effectiveness of anti-CD20 therapy in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) strengthens the role of B cells in the pathogenesis. Therefore, we aimed to investigate the CD180 expression of peripheral blood B cell subsets in NMOSD and MS patients and analyze the levels of natural anti-citrate synthase (CS) IgG autoantibodies and IgG antibodies induced by bacterial infections reported to play a role in the pathogenesis of NMOSD or MS.

Methods: We analyzed the distribution and CD180 expression of peripheral blood B cell subsets, defined by CD19/CD27/IgD staining, and measured anti-CS IgM/G natural autoantibody and antibacterial IgG serum levels in NMOSD, RRMS, and healthy controls (HC).

Results: We found decreased naïve and increased memory B cells in NMOSD compared to MS. Among the investigated four B cell subsets, CD180 expression was exclusively decreased in CD19+CD27+IgD+ nonswitched (NS) memory B cells in both NMOSD and MS compared to HC. Furthermore, the anti-CS IgM natural autoantibody serum level was lower in both NMOSD and MS. In addition, we found a tendency of higher anti-CS IgG natural autoantibody levels only in anti-Chlamydia IgG antibody-positive NMOSD and MS patients.

Conclusions: Our results suggest that reduced CD180 expression of NS B cells could contribute to the deficient natural IgM autoantibody production in NMOSD and MS, whereas natural IgG autoantibody levels show an association with antibacterial antibodies.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Autoantibodies / immunology*
  • B-Lymphocyte Subsets / immunology*
  • Cells, Cultured
  • Citrate (si)-Synthase / immunology*
  • Down-Regulation
  • Female
  • Humans
  • Immunoglobulin M / metabolism
  • Male
  • Memory B Cells / immunology*
  • Middle Aged
  • Multiple Sclerosis / immunology*
  • Neuromyelitis Optica / immunology*
  • Toll-Like Receptors / genetics
  • Young Adult

Substances

  • Antigens, CD
  • Autoantibodies
  • CD180 protein, human
  • Immunoglobulin M
  • Toll-Like Receptors
  • Citrate (si)-Synthase