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Lupus Research Update: 2006 Volume 3

Volume 3, 2006 - Online Edition | In This Issue


Meet the Investigator >
Pilot Grant Program >
Research Results - Using Cholesterol Levels to Screen for Worsening Lupus-Related Kidney Disease >
Research Results - New Genetic Findings Linked to Lupus in Mouse Models >
Research Results - Rituximab for Lupus Shows Promise >
Research Results - New Target for Treatment Identified >
Advocacy Update - Senator Charles Schumer Champions Lupus Research >
Beyond the Research - The ALR Walks Nationwide >
Drug Research and Development News >

Research Results - New Genetic Findings Linked to Lupus in Mouse Models

Although science strongly suggests that the development of systemic lupus erythematosus (SLE) is the result of complex interactions between genetics and the environment, we have very little information on lupus-related genes and how they function. Now twoALR-funded researchers at the University of Texas’ Southwestern Medical Center in Dallas have pinpointed two genetic mutations in mice that contribute to the development of the disease.

In one study published in the June 15, 2006 issue of Science, a research team led by Chandra Mohan, MD, PhD, Professor of Internal Medicine, found that a defect in the Ly108 gene allows B cells that react against “self,” and divide rather than die in response to signals that would normally maintain B cell tolerance. Thus, these anti-self B cells go on to make the autoantibodies that characterize lupus.

Since it is well known that loss of B cell tolerance is a hallmark of SLE, identifying this gene provides an important clue as to the underlying mechanism responsible for that process, said Dr. Mohan.

In the second study, published in the June 27, 2006 issue of the Proceedings of the National Academy of Sciences, a research team led by Edward Wakeland, PhD, professor of immunology and director of UT Southwestern’s Center for Immunology, found that mice that died from lupus carried twice the normal amount of copies of the mutated receptor gene Tlr7. This mutant gene is called Yaa (for Y-linked autoimmune acceleration), since it is located on the male Y chromosome. Similar results have been found by a group headed by Silvia Bolland of the National Institutes of Health. Previous research showed the Yaa dramatically accelerates the progression of SLE. When it interacts with Ly108, it triggers the mechanisms that lead to the deadly form of lupus by causing further immune system malfunction.

Both findings, if also identified in humans, could provide new molecular targets for more specific SLE treatments and for the development of diagnostic tests.

Kumar KR, Li L, Yan M, Bhaskarabhatla M, Mobley AB, Nguyen C, Mooney JM, Schatzle JD, Wakeland EK, Mohan C. Regulation of B cell tolerance by the lupus susceptibility gene Ly108. Science. 2006 Jun 16;312(5780):1665-9. Subramanian S, Tus K, Li QZ, Wang A, Tian XH, Zhou J, Liang C, Bartov G, McDaniel LD, Zhou XJ, Schultz RA, Wakeland EK. A Tlr7 translocation accelerates systemic autoimmunity in murine lupus. Proc Natl Acad Sci U S A. 2006 Jun 27;103(26):9970-5. Pisitkun P, Deane JA, Difilippantonio MJ, Tarasenko T, Satterthwaite AB, Bolland S. Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication. Science. 2006 Jun 16;312(5780):1669-72.

Just the Facts

What the study showed:
New genetic mutations associated with lupus

What they mean:
Potential new markers for drug development

What's next:
Identifying same genetic mutations in humans and continuing to gain a better understanding of the genes involved

ALR funding:
$2.5 million to date


1.5 million

people in the U.S. have Lupus.

90 million

dollars committed to lupus research by the Alliance for Lupus Research.


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