Ohio State researchers win major grant to study lupus

COLUMBUS, Ohio -- A multidisciplinary team of researchers at The Ohio State College of Medicine and Public Health has received a $4.6 million dollar grant from the National Institutes of Health (NIH) to study the causes and progression of systemic lupus erythematosus (SLE), better known as lupus. Lupus is an autoimmune disease, where the body's own immune system attacks multiple organs, including the skin, joints, kidneys, lungs, heart, and brain. Both men and women may get lupus, but it is most commonly found in young women under the age of 45, and more frequently among Blacks, Asians, and Hispanics than Caucasians.

Dr. Lee Hebert, director of the division of nephrology and principal investigator of the grant, says the goals of the study include the identification of the genetic factors which affect whether a patient's lupus will be mild or severe, the clinical and environmental factors that trigger lupus relapse, and the best means to predict when a relapse will occur.

"There is so much about lupus that is poorly understood," says Hebert. "For example, it is widely believed that certain things like stress, infections, hormones, or exposure to sunlight or other sources of ultraviolet radiation can trigger a relapse, but the evidence is largely anecdotal."

In addition, he says, most theories about the cause of lupus center on excessive autoantibody production. "We believe a more fundamental role may be played by something called immune complex clearance, where the body is unable to rid itself of destructive residues which build up in tissues and create inflammation."

The Ohio State team will be working closely with community-based physicians and hospitals across the state to recruit at least 500 patients and their families to the study. "Lupus is a difficult disease to diagnose and treat, and the course of the disease can vary widely, depending upon a number of genetic and environmental factors," says Hebert. "Our job is to identify specific genetic and environmental changes that affect how the disease is going to act. In order to do this, we need to test whole families."

Patients recruited to the study will receive the highest level of care, and will remain under the direct care of their family physician, but will make periodic visits to Ohio State for genetic testing and laboratory work.

Hebert says almost all of the nephrologists and rheumatologists in central Ohio have agreed to participate in the study.

"We are extremely proud of Dr. Hebert's work," says Dr. Fred Sanfilippo, senior vice president of Health Sciences and dean of the College of Medicine and Public Health at OSU. "Competition for NIH program project grants is extraordinarily intense. Successful applicants must demonstrate multidisciplinary strength in basic science and clinical application. This is clear recognition of our record of academic excellence."

The grant, to be administered over a five-year period, includes support for four major projects focused on understanding one of the most dangerous complications of lupus, SLE nephritis. The individual projects within the grant include:

Project 1, under the direction of Dr. Daniel Birmingham, associate professor of internal medicine and pathology, will assess the various factors that lead to SLE nephritis.

Project 2, under the guidance of Dr. Chack Yung Yu, associate professor of molecular immunology, will specifically analyze the role of various genes in SLE nephritis.

Project 3, under the leadership of Dr. Brad Rovin, associate professor of medicine and pathology, will examine chemokine regulation in nephritis, and finally, in Project 4, Dr. Hebert will take the lead in determining the broad predictors of lupus relapse.