Do particular antibody genes recognize gray matter cellular targets? (HUM2P.338)

My lab’s recent work on the antibody genetics of multiple sclerosis (MS) patients has led to the astonishing discovery that patterns of mutation accumulation into the antibody genes of B cells in the central nervous system (CNS) of MS patients are unique and can be used to predict clinically isolated syndrome (CIS) conversion to MS with 94% accuracy. This Antibody Gene Signature (AGS) is a novel, potentially diagnostic biomarker that is currently in clinical trials and heralds the advent of antibody genetics as a means to categorize patients early in their disease course in order to provide prompt treatment and prevent extensive CNS damage. Our goal for this project was to determine what antibodies expressed by these B cells from MS patients reacted against. We cloned and expressed more than 30 antibodies that contain the AGS-MS from cerebrospinal fluid derived single B cells of MS and CIS patients, and tested their capacity to bind to brain tissue. We found that these AGS-MS enriched antibodies bind to neurons and astrocytes that reside in the brain gray matter tissue with high specificity. Some of these antibodies recognize both neurons and astrocytes in the gray matter, whereas others are specific for a single cell type. We hypothesize that AGS-enriched rhAbs and B cells expressing these antibodies could be participating in gray matter disease pathology in both early CIS and later MS stages.