Two Genetics Discoveries in Lupus Reported

Ideas with Broad Therapeutic Implications First Funded by the Lupus Research Institute

June 16, 2006 - New York – Major discoveries that shed new light on how two different genes contribute to systemic lupus erythematosus ("lupus") have been announced. Building on work initially funded by the Lupus Research Institute, the findings published in the prestigious journal, Science, offer real hope for better understanding and treating this complex disease that affects more than 1.5 million Americans.

In lupus, for reasons that scientists are just now figuring out, the immune system turns on itself and produces antibodies that can attack virtually any healthy organ or tissue, from the kidneys to the brain, heart, lungs, skin, joints and blood. Current treatments for lupus are highly toxic.

"Both of these [Science] papers provide important insight into genetic factors that can contribute to the development of lupus, and therefore, potential new therapeutic targets," said Ann Marshak-Rothstein, PhD, professor of microbiology at Boston University School of Medicine.

New Clues to What Makes a Person Prone to Lupus

Silvia Bolland, PhD, who received a grant from the Lupus Research Institute in 2001, is the lead author of the Science study that for the first time characterizes how having a gene called the 'Y-linked autoimmune accelerator,' or Yaa, makes the body more susceptible to lupus.

Specifically, she shows that Yaa is a duplicated copy of a gene that makes an RNA receptor known as TLR7. In mice with the extra copy of the TLR7 gene, cells produce twice as much of the RNA receptor, which make the mice more sensitive to RNA-associated proteins and more likely to mount a harmful autoimmune response to the body's own RNA.

"Bolland's findings show that one extra copy of the gene is enough to predispose to severe autoimmunity—direct evidence that minor genetic mutations, small differences in expression, are important," said Mark Shlomchik, M.D., Ph.D., professor of laboratory medicine and immunobiology at Yale University School of Medicine and co-chair of the Lupus Research Institute's Novel Research Task Force that selects research projects to fund.

"This study provides new understanding of how this gene works and insight into the genetic basis of lupus, in other words, why lupus runs in families," he pointed out. "It also highlights TLR7 as another potential target for lupus therapies."

Subsequent funding from the National Institutes of Health made it possible for Bolland to expand on her original Lupus Research Institute research, and she now conducts lupus research at the National Institute of Allergy and Infectious Diseases.

New Explanation for Immune System Breakdown in Lupus

The Science paper of University of Texas Southwestern Medical Center professor Edward K. Wakeland, PhD, who also received a Lupus Research Institute grant in 2001, shows that in lupus-prone mice, having a so-called receptor gene—Ly108—contributes to a breakdown in controlling the white blood cells of the immune system that produce antibodies, called B cells. This breakdown causes the B cells to go haywire and start producing antibodies to elements of the mouse's own body (such as DNA), thereby leading to many of the manifestations of lupus.

"My initial funding from the Lupus Research Institute played a pivotal role in making these findings possible," said Wakeland. "With that early funding we developed an antibody that was critical in helping Dr. Chandra Mohan [M.D., Ph.D., and lead study author] and the team determine the function of Ly108 in this study. Moving forward, the antibody will continue to be a valuable tool for the research community."

"This is the crux of the Lupus Research Institute's mission,' noted Lupus Research Institute President and CEO, Margaret Dowd. "To identify, fund and champion scientists with new ideas so that they can validate their hypotheses and establish the data needed to advance novel concepts in lupus research."

Role of the Lupus Research Institute

The Lupus Research Institute is the world's only first-tier novel lupus research funding organization, bridging the chasm between promising new ideas for curing, preventing and treating lupus and next-tier sources of government and private research funding. It provides grants to researchers with novel, out-of-the-box ideas for addressing lupus.

The urgent need for new approaches for the disease, for which there have been no major treatments approved in the last 40 years, led to the Institute's creation in 2000. Founded and funded by lupus patients and their families, and developed with the help of leading lupus scientists, the Institute now backs the largest number of privately funded scientific investigators in lupus nationwide, to date supporting 57 lupus researchers with more than $15 million from generous donors.

To learn more about lupus and the Lupus Research Institute, visit