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Abstract Details

The Downstream Implications of Somatic Hypermutation in Multiple Sclerosis: What Are the Cellular Targets of Antibodies Produced by MS Patient CSF Derived B Cells?
MS and Related Diseases
P03 - (-)
223
BACKGROUND: We have recently demonstrated that B cells from the cerebrospinal fluid of MS patients have a distinct pattern of somatic hypermutation (SHM) in their antibody genes. We call this specific SHM pattern the Antibody Gene Signature for MS (AGS-MS). The specific regions of hypermutation with the VH4 region would be expected to alter antigen binding characteristics of the antibodies.
DESIGN/METHODS: We cloned and expressed 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 tissue with high specificity. Confocal microscopy confirms that neurons and astrocytes in the brain tissue are recognized by these antibodies. Some of these antibodies recognize both neurons and astrocytes, whereas others are specific for a single cell type.
CONCLUSIONS: This study is the first to discern the antigenic targets of hypermutated B cells in patients with RRMS and CIS. The data expands upon our previous observations that B cells from MS patients have a unique pattern of somatic hypermutation. This study shows that the pattern of hypermutation leads to specific anti-neuronal and anti-astrocytic antibodies that may have pathologic significance.
Authors/Disclosures
Ann Ligocki
PRESENTER 		No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Benjamin M. Greenberg, MD, FAAN (UT Southwestern Medical Center) Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Greenberg has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Sanofi/Genzyme. Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech/Roche. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Signant. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Greenberg has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Clene. Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for IQVIA. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abcuro. Dr. Greenberg has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Siegel Rare Neuroimmune Association. Dr. Greenberg has or had stock in GenrAb.Dr. Greenberg has or had stock in Clene.Dr. Greenberg has received intellectual property interests from a discovery or technology relating to health care. Dr. Greenberg has received publishing royalties from a publication relating to health care.
Elliot M. Frohman, MD, FAAN Dr. Frohman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Janssen. Dr. Frohman has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Janssen. Dr. Frohman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Up To Date. Dr. Frohman has received publishing royalties from a publication relating to health care.
No disclosure on file
Nancy Monson (University of Texas Southwestern) Nancy Monson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Nancy Monson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GenrAb, Inc.. Nancy Monson has stock in GenrAb, Inc.. The institution of Nancy Monson has received research support from NIH. Nancy Monson has received intellectual property interests from a discovery or technology relating to health care.