NIH Program Project: Genetic and Clinical Risk Factors for Human SLE Nephritis

 If you could change one thing about lupus, what would it be?  Probably you would wish to stop lupus altogether.  Unfortunately, at this time that is not possible because lupus is in one’s genes.  OK, make another wish.  If you wished to make lupus more predictable so that you could better prepare for the ups and downs of lupus, that wish might be granted by the scientists and physicians of the Ohio SLE Study.

The Ohio SLE Study is the collaboration between investigators at The Ohio State University working and virtually all of the rheumatologists and nephrologists in Central Ohio.  They are seeking ways to “tame” lupus by being able to predict when it is about to flare.  This study is one of the four projects within the $4.6 million NIH Program Project titled “Genetic and clinical risk factors for human SLE nephritis”.  The study within the Program Project that seeks to identify the clues for SLE relapse is titled “Pathogenesis of SLE relapse”.

Over 100 SLE patients with recurrently active disease are participating in the Ohio SLE Study.  The patients are drawn from throughout Central Ohio.  They are followed meticulously in collaboration with their own rheumatologists and nephrologists in an attempt to identify the environmental, clinical, and genetic factors that predict SLE flare and its severity.  This aspect of the NIH program project is being led by Lee A. Hebert, MD and Kevin Hackshaw, MD.

The remainder of the NIH program project is devoted to studying SLE patients and their families to identify genetic factors to better understand why only some SLE patients develop the severe problems of SLE nephritis.  To date we have studied more nearly 500 SLE patients and their family members.  Already we have identified several urine markers that appear to predict adverse outcome in SLE.  This work is being led by Dr. Brad Rovin and involves a measurement of chemokines in urine principally IL-8 and MCP-1.  We have also  identified aberrations in receptors on red cells that bind components.  These receptors appear to be shed and may protect against kidney disease.  This work is being led by Dr. Daniel Birmingham.  Dr. Chack Yung-Yu is undertaking detailed genetic studies of the relationship between polymorphisms of C4 and the presence of lupus particularly with kidney involvement.  Certain of the C4 genes appear to be strong risk factors for developing severe lupus, including that with kidney disease.  This work requires sophisticated statistical analyses.  This aspect of our work is being led by Dr. Haikady “Raj” Nagaraja and assisted by Dr. Robert Rice of the Clinical Research Center. 

It is our expectation that this work, taken together, will provide major contributions to the understanding and management of human SLE.