IgA Nephropathy Research



Nephrology Research & Training Center (NRTC)

The history and mission of the Nephrology Research and Training Center (NRTC) established in 1976, was funded as a University-wide Pilot Developmental Center in October 2006 and was recognized as a full University-wide Interdisciplinary Research Center effective October 2008. In 1998, the NRTC was strengthened by the provision of an endowment, the proceeds of which were targeted to support its training and research activities. Recognizing the importance of enhancing the research portfolio of the NRTC, Dr. Anupam Agarwal was recruited as the Director of the Center in November 2003. In November, 2009, Dr. Paul Sanders was appointed to the position of Director, with Dr. Agarwal taking a role as the Associate Director.

Since 2006, the renewed mission of the NRTC has been to provide a comprehensive interdisciplinary infrastructure and environment to support the kidney-related research continuum from molecular pathways to model systems to man. The particular emphasis of this Center will be to focus on projects/experimental strategies that integrate basic concepts and clinical insights into translational research. Through educational outreach programs, relevant data will be shared with the community so as to improve health and well-being of those affected by kidney disease and hypertension and increase the number of organs available for renal transplants through public awareness.

NRTC & IgA Nephropathy Research

“If we could identify the patients at risk, we could manage them more effectively to keep the inflammatory processes at bay with anti-hypertension and other medications,” says Professor Bruce A. Julian, MD, Division of Nephrology. Dr. Julian has had a career-long interest in IgA nephropathy since discovering the disease in two first cousins of a Kentucky family in 1982.

He and Robert J. Wyatt, MD, then in the Department of Pediatrics at the University of Kentucky, established the hereditary nature of the disease with their analysis of the Kentucky family, which was rife with IgA nephropathy. “We developed the family pedigree and began to write it up on weekends on an old typewriter, using my kitchen table as a desk,” Dr. Julian says. In 1985, shortly after Dr. Julian moved from Lexington, Kentucky, to join the UAB faculty, the two physicians’ study was published in the New England Journal of Medicine (NEJM). They have coauthored 29 scientific papers since that time.

At UAB Dr. Julian has partnered over the years with basic scientists in the Department of Microbiology. “A succession of microbiologists and immunologists has been great to work with, beginning with Jiri Mestecky,” Dr. Julian says. Professor of Microbiology Jiri Mestecky, MD, PhD, and colleagues Professor of Medicine Milan Tomana, PhD, and Professor of Microbiology Zina Moldoveanu, PhD, have been the most constant members of the laboratory group, and they were joined 12 years ago by Associate Professor of Microbiology Jan Novak, PhD.

UAB Research Findings

In the past 25 years, UAB clinical and basic scientists have demonstrated that IgA nephropathy is an autoimmune disease in which molecules of IgA1 are deficient in a sugar, galactose, and behave as an autoantigen. These discoveries showed:

Sera of healthy controls and patients with IgA nephropathy contain antibodies recognizing galactose-deficient IgA1, driving formation of immune complexes.
Serum levels of galactose-deficient IgA1 are heritable.
The capacity of circulating immune complexes with galactose–deficient IgA1 to active human mesangial cells in culture.
The chromosomal locus of a gene responsible for the familial nature of the disease for some patients.
With seed funding from the IgA Nephropathy Foundation of America, Dr. Novak’s lab is preparing to use its assay to see if relatively higher levels of galactose-deficient IgA1 in the blood results in a greater risk of a diagnosis of IgA nephropathy later in life. Such a test also would provide important information for a noninvasive test for diagnosis, monitoring the clinical course or response to treatment, and selection of individuals appropriate to consider donation of a kidney to an affected relative.

The hypothesis proved strong in initial testing. “Dr. Steve Olson, a nephrologist in the US Army at Walter Reed Medical Center in Washington, DC, contacted us based on our published work and offered to provide serial serum samples from the Department of Defense repository for our studies. These specimens had been collected from personnel at induction into the service and at frequent subsequent intervals. Some individuals over the years developed various types of kidney diseases, including IgA nephropathy,” Dr. Julian says. “In testing a few samples, we found that the blood level of galactose-deficient IgA1 was higher in individuals who developed IgA nephropathy than in those who developed other types of renal disease. Furthermore, the level was significantly higher years prior to the appearance of urinary abnormalities that prompted a diagnostic renal biopsy. We are very grateful to have access to these samples.”

The chance for more extensive testing came with an invitation from the advocacy group for Drs. Julian, Novak and Wyatt to present their case for funding. The three spent a Saturday in a Nashville, Tennessee hotel conference room detailing their project.

“The foundation had previously worked with Dr. Wyatt, now at the University of Tennessee, Memphis and learned of us from him, but they obviously had looked into our work for themselves. We were glad to have the opportunity to present the work to them and that they funded the next phase,” Dr. Julian says. “Based on our results, we hope to develop a non-invasive blood test that will improve the care of patients with IgA nephropathy.”