Volume 1, 2008 | IN THIS ISSUE

> ALR Funded International Consortium Identifies Genes Linked to Lupus
> The Faces of Lupus: Eddie Kennison, Kansas City Chiefs
> Meet the Investigator — Mary K. Crow, M.D., Named Chair of Scientific Advisory Board
> Research Results — New Clue in the Survival of Autoimmune B Cells
> Research Results — Narrowing Down a Lupus-Related Gene
> Research Results — Finding Hidden Clues to Children's Lupus Nephritis
> Research Results — Finding Ways to a Safer Pregnancy for Women with Lupus
> Drug Research and Development News — Atacicept (TACI-Ig), CPG 52364, and Rituximab (Rituxan)
> Leaving a Legacy

ALR Funded International Consortium Identifies Genes Linked to Lupus

Just two years after the Alliance for Lupus Research (ALR) organized and funded the International Systemic Lupus Erythematosus Genetics (SLEGEN) Consortium, the consortium has published its first major results, identifying several genes linked to lupus and underscoring the importance of genetic variants in diseases that affect immune function. The findings were published in the January 20 issue of the journal Nature Genetics.

"These results suggest biologic pathways that help us understand the condition better and suggest additional genetic and non-genetic triggers," said SLEGEN co-Director Carl Langefeld, Ph.D. "In addition, they will help delineate the genetic distinctions between rheumatoid arthritis, lupus and other autoimmune diseases, which could lead to earlier, more accurate diagnoses."

"The SLEGEN study is a model for collaborative genetic research," said Mary K. Crow, M.D., who chairs the ALR's Scientific Advisory Board and is a professor of medicine and the Benjamin M. Rosen Chair in Immunology and Inflammation Research at the Hospital for Special Surgery (HSS) in New York City (more on Dr. Crow's appointment on page 1). "The ALR's approach of supporting investigations targeted toward developing new therapies for people with lupus is unique and meaningful." Dr. Langefeld, who directs the Center for Public Health Genomics at Wake Forest University in Winston-Salem, N.C., also noted how satisfying the study results were. "This is one of those things that, at the end of your career, you can look back on and smile because you believe it will make a real difference."

The study found strong evidence of association with multiple single nucleotide polymorphisms (SNPs) in three genes: ITGAM; KIAA1542; PXK; and at SNP rs10798269, a DNA unit not found within any known gene, explained SLEGEN co-Director John B. Harley, M.D., Ph.D. SNPs are chromosome locations on which a single unit of DNA may vary from one person to another.

The results also suggest links between lupus and nine other genes. "I would have been satisfied with finding one gene," said Dr. Harley, who heads the Arthritis & Immunology Research Program at the Oklahoma Medical Research Foundation in Oklahoma City. "The fact that we present 13 strong candidates, supported by data that are 99 percent accurate, is tremendous.

Researchers studied the DNA of more than 6,700 women, including individuals with lupus, their family members and control subjects. They scanned the entire genome for more than 317,000 SNPs to identify those linked to lupus. "SLEGEN's purpose is to do the genomics," Dr. Harley said. "The mechanism of the disease by which these genes cause lupus will be seized upon by scientists who are expert in those pathways to develop new strategies for prevention and therapy and reduce the burden of suffering this disease causes."

ALR funding for SLEGEN: $2.25 Million