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.
Highlights
Multiple sclerosis (MS) is a chronic, progressive, neuroinflammatory disease characterized by immune-mediated inflammation, demyelination, and axonal damage in the central nervous system (CNS) [1,2,3]
We found no significant differences in the percentage of total CD19+ B cells and distribution of B cell subsets in neuromyelitis optica spectrum disorder (NMOSD) or MS compared to healthy controls (HC)
This is in agreement with previous findings [27,28,29] reporting no significant differences in the distribution of naïve and memory B cell subsets in MS compared to HC
Summary
Multiple sclerosis (MS) is a chronic, progressive, neuroinflammatory disease characterized by immune-mediated inflammation, demyelination, and axonal damage in the central nervous system (CNS) [1,2,3]. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the CNS, primarily affecting the optic nerves and the spinal cord, leading to blindness and paralysis [4,5,6,7]. NMOSD was only recognized as a distinct disease entity and separated from MS over the past 10 years with the discovery of a unique biomarker, autoantibodies against the aquaporin-4 (AQP4) molecule [8]. 10-25% of patients with a clinical diagnosis of NMOSD remain AQP4 antibody-negative [9]. The clinical success of antiCD20 antibodies in the treatment of MS and NMOSD [11, 12] underlines the important role of B cells in disease initiation and progression.
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