Approximately one-third of people with lupus develop nephritis, a complication that can cause kidney failure and sometimes requires chronic dialysis or transplantation.
Most research suggests that antibodies in the kidney play a role in the development of kidney failure in lupus, but exactly how this occurs is unclear.
“It starts with antibodies, there's no doubt about it,” Dr. Deshmukh says. “But antibody alone is not sufficient, you have to have T cells going into the kidney,” he says. T cells regulate immune responses in lupus.
Using carefully selected mouse models, Deshmukh and colleagues investigated whether it is antibodies alone that form the basis for kidney disease in lupus as well as where, when, and how T cells come into play.
Through the course of their research, Dr. Deshmukh and colleagues not only gathered substantial evidence to support their original hypothesis, but went on to work on a new mouse model of lupus in which they can test new approaches to target drugs to the kidney (immunoliposomes).
Their findings “change the perceived role of autoantibodies in the disease” he says. “If we find antibodies in the kidney, we jump to the conclusion that it's lupus nephritis, but our study will show that you can have antibodies in kidney and still be healthy because the damage starts with T cells.”
And while not included in the current grant, Dr. Deshmukh and colleagues have already started looking at drugs that can prevent T-cell mediated damage of the kidneys.
With a co-investigator, Dr. Deshmukh now has funding to explore the development of targeted drug delivery system using immunoliposome nanoparticles.
Genetic complementation results in augmented autoantibody responses to lupus-associated antigens. Sim DL, Bagavant H, Scindia YM, Ge Y, Gaskin F, Fu SM, Deshmukh US. J Immunol. 2009 Sep 1;183(5):3505-11
SmD peptide induces better antibody responses to other proteins within the small nuclear ribonucleoprotein complex than to SmD protein via intermolecular epitope spreading. Deshmukh US, Bagavant H, Sim D, Pidiyar V, Fu SM. J. Immunol. 2007 Feb 15;178(4):2565-71
Role for nephritogenic T cells in lupus glomerulonephritis: progression to renal failure is accompanied by T cell activation and expansion in regional lymph nodes. Bagavant H, Deshmukh US, Wang H, Ly T, Fu SM. J. Immunol. 2006 Dec 1;177(11):8258-65.
New insights from murine lupus: disassociation of autoimmunity and end organ damage and the role of T cells. Bagavant, H. and Fu, S.M. Deshmukh, U.S, Bagavant, H., Lewis, J., Gaskin, F., Fu, S.M. Curr. Opin. Rheumatol 2005 17:523-528.
Role of anti-DNA antibodies in the pathogenesis of lupus nephritis. Deshmukh US, Bagavant H, Fu SM. Autoimmun Rev. 2006 Jul;5(6):414-8. Epub 2005 Dec 7.
In 2006, Dr. Deshmukh won a $1.65 million NIH grant continue this work, and in 2009 received a two-year Alliance for Lupus Research (ALR) award of $499,780 to futher explore ‘modulating renal responses: a novel therapeutic approach to lupus nephritis” (as co-investigator).
Rev. July 2010