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Reduction in antibody gene rearrangement in B cells related to type 1 diabetes, lupus
Date:12/23/2008

PHILADELPHIA More drafts usually mean a better product and so it also seems to go with the human immune system. As B cells develop, genes rearrange to allow antibodies to recognize different foreign invaders or pathogens. But sometimes antibodies are created that recognize and attack the body's own cells. These self-reactive antibodies, like early drafts of a manuscript, must be edited into versions that won't attack self. This process is called receptor editing and is important for central or early B cell tolerance, which occurs while B cells are still developing in the bone marrow. A research team led by Nina Luning Prak, M.D., Ph.D, Assistant Professor in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania School of Medicine, has discovered that this editing process may go awry in people with certain types of autoimmune diseases.

Prak and her colleagues, including the study's first author, Penn MD-PhD student Anil Panigrahi, observed that the amount of antibody edits in the development of B cells is related to two types of autoimmune disease, lupus and type 1 diabetes. The findings, which appeared online this month in the Journal of Experimental Medicine, have implications for new tests and more personalized treatments for autoimmune diseases.

The investigators found a lower level of antibody editing in mouse models and in blood samples from lupus and diabetes patients. In the samples from autoimmune patients, 30 percent had low editing levels, a high proportion, but also indicative that not all autoimmunity is caused by errors in editing. A targeted, personalized approach may be necessary to treat these complex diseases, according to the researchers. New assays derived from this study to assess the level of editing may help direct appropriate therapies.

"Right now we have a very crude approach to treating autoimmunity: depleting or inactivating circulating B or T cells wholesale," expl
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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