EP10
Do Particular Antibody Genes Recognize Gray Matter Cellular Targets?
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 (http://www.prnewswire.com/news-releases/diogenix-msprecise-identifies-early-stage-patients-with-multiple-sclerosis-177841251.html) 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.
Objectives:
Our goal for this project was to determine what antibodies expressed by these B cells from MS patients reacted against.
Methods:
We cloned and expressed more than 30 antibodies that contain the AGS-MS from cerebrospinal fluid derived single B cells of patients with clinically definite MS, patients with one attack of optic neuritis and patients with one attack of transverse myelitis, and tested their capacity to bind to brain tissue.
Results:
We found that these AGS-MS enriched antibodies from both established MS patients and patients at high risk to develop MS, bind to brain gray matter tissue with high specificity, but do not bind to mouse or human brain white matter tissue. Confocal microscopy confirms that neurons and astrocytes in the brain gray matter tissue are recognized by these antibodies. Some of these antibodies recognize both neurons and astrocytes in the gray matter, whereas others are specific for a single cell type.
Conclusions:
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.