An appraisal of antigen identification and IgG effector functions driving host immune responses in multiple sclerosis.

Increased immunoglobulin G (IgG) antibodies and oligoclonal bands (OCB) are the most characteristic features of multiple sclerosis (MS), a neuroinflammatory demyelinating disease with neurodegeneration at chronic stages. OCB are shown to be associated with disease activity and brain atrophy. Despite intensive research over the last several decades, the antigen specificities of the IgG in MS have remained elusive. We present evidence which supports that intrathecal IgG is not driven by antigen-stimulation, therefore provide reasoning for failed MS antigen identification. Further, the presence of co-deposition of IgG and activated complement products in MS lesions suggest that the IgG effector functions may play a critical role in disease pathogenesis.