IgA Deficiency Exacerbates an Animal Model of Multiple Sclerosis Induced with Theiler’s Virus

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammatory demyelination and axonal degeneration in the central nervous system (CNS) and has been linked to viral infections. Theiler’s murine encephalomyelitis virus (TMEV) infection in SJL/J mice has been widely used as a viral model of MS, since TMEV-infected mice develop MS-like demyelination and axonal degeneration with viral persistence in the CNS. In the TMEV model, we previously demonstrated upregulation of immunoglobulin (Ig) A-related genes in the CNS, as well as IgA deposition and IgA-positive cell infiltration in demyelinating lesions. Although IgA has been implicated in the pathophysiology of MS, its precise role remains unclear. To determine the role of IgA in the TMEV model, we established IgA knockout (KO) mice on the SJL/J background; IgA KO mice lacked serum IgA and exhibited altered gut microbiota compositions. We found that TMEV-infected IgA KO mice developed more severe neurological signs than wild-type (WT) mice. IgA KO mice also had more severe inflammatory demyelination with higher levels of viral persistence and T cell infiltration in the CNS than WT mice. Immunologically, IgA KO mice mounted TMEV-specific lymphoproliferative responses and serum anti-viral antibody isotype titers, except for IgA, which were comparable to WT mice. Interleukin (IL)-17 and IL-10 productions were higher in IgA KO mice than in WT mice. Thus, IgA could play a protective role in the TMEV model in WT mice; IgA deficiency-mediated gut dysbiosis may contribute to enhanced immunopathology in IgA KO mice.