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Researchers identify novel pathophysiologic mechanism responsible for autoimmunity
Date:4/25/2011

within traditionally defined clinical entities, such as rheumatoid arthritis or systemic lupus erythematosus. By shotgun sequencing of DS affinity-enriched proteomes extracted from cell lines, they identified more than 200 autoantigens, both novel and previously linked to autoimmunity, including several well-known families of autoantigens related to the nucleosome, ribonucleoproteins, the cytoskeleton and heat shock proteins. We were able to capture the entire known human auotantigen-ome and then some more in a single experiment," explained senior author Michael Roehrl, MD, PhD, an assistant professor of pathology and laboratory medicine at BUSM.

The studies revealed that noncovalent DS-antigen complexes have the unique capability of expanding B-1a. "On the basis of our findings, we propose that DS forms complexes with autoantigens presented by apoptotic or dead cells and that these complexes promote the positive selection and expansion of autoreactive CD5_ B cells and the secretion of autoantibodies," he added.

"It has been a longstanding puzzle why only a small subset (1-2 percent) of all human proteins can become functional antibody targets in autoimmune diseases. Our theory offers a plausible answer to this ontogenic question central to autoimmunity by showing that affinity to DS may be a unifying principle of autoantigens," stated Roehrl.

The researchers believe that further investigation of the molecular activities of DS and DS-binding proteins will lead to a more precise understanding of the molecular mechanisms driving B-1a cell activation and thus autoimmune disease. Furthermore, Roehrl's laboratory is already using the new discoveries to develop personalized molecular serum testing for patients with autoimmune diseases, an area of medicine that "has not seen significant advances in a very long time and that was ripe for a real breakthrough" according to Roehrl.


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Contact: Gina DiGravio
gina.digravio@bmc.org
617-638-8480
Boston University Medical Center
Source:Eurekalert

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