Antigen reactivity of B cells from patients at risk to develop Multiple Sclerosis demonstrates a specific somatic mutation pattern. (159.28)

Abstract Multiple Sclerosis (MS) is the leading disease of the central nervous system and a significant, costly cause of disability in young adults. Patients at risk for MS often present with a single demyelinating event, typically called a “clinically isolated syndrome” (CIS). A CIS can occur in the brain, spinal cord (Acute Partial Transverse Myelitis, APTM), or optic nerve (Optic Neuritis, ON). Our laboratory discovered a unique pattern of antibody gene mutation accumulation (i.e. antibody gene signature, or “AGS”) that is exclusive to B cells from the cerebrospinal fluid (CSF) and brain lesions of MS patients and CIS patients that develop MS in the future. Our goal for this study was to determine whether CIS and MS patient B cells that carry this pattern of somatic hypermutation accumulation in their antibody genes react to brain tissue. Thirty-four antibody genes of B cells isolated from the CSF of MS and CIS patients carrying this AGS pattern were cloned into antibody expression vectors to generate recombinant full-length human antibodies (rhAbs). Preliminary DAB staining using a subgroup of these rhAbs on cryo-sectioned mouse brain demonstrates binding to CNS tissue. Cortical staining of varied intensities was found among the rhAbs tested. Patterns of staining and details of antigen reactivity will be presented. This result provides promise in continuing to identify the auto-antigens that are recognized by the AGS B cells shared among patients at risk to convert to MS.