Local factors contributing to pathogenesis of proliferative lupus nephritis
Dr. Fu’s work hopes to turn traditional views on lupus nephritis upside down and could change how it is treated dramatically. He hypothesizes that the kidney itself can drive kidney disease, not as a complication of systemic lupus, but as an independent process. His team has shown that kidney cells help promote development of kidney failure because they release molecules such as C1q, a protein that helps activate a part of the immune system.
What this study means for people with lupus:
Dr. Fu’s study aims to reveal how these C1q molecules released by kidney cells determine which patients develop kidney failure. They hope to identify whether targeting C1q offers a potential therapy and if measuring the levels of this molecule in the urine can help diagnose severity of kidney damage and monitor response to treatment
Proliferative lupus glomerulonephritis (PLGN) often leads to end stage renal failure. Current therapies are not effective in many patients. Biomarkers for diagnosis and monitoring responses to therapy are lacking. This application investigates local tissue factors that contribute to the progression of PLGN. We have shown that autoimmunity and end organ damage are under separate genetic control. This new paradigm focuses us on the role of targeted tissue in PLGN. Our new observation is that C1q is expressed by podocytes in late stages of GN in mouse and in class IV PLGN patients with urinary C1q positive podocytes. We plan to interrogate the role of podocyte-made C1q and the interactions between this C1q and intraglomerular cytokines. We will determine whether C1q deficiency in podocytes will suppress the development of PLGN, demonstrate the role of locally-synthesized cytokines in the induction of C1q synthesis by podocytes in PLGN and ascertain the usefulness of C1q in urinary podocytes as a biomarker in the diagnosis of class IV PLGN. The results of these studies will provide insights to the contribution of local factors to the pathogenesis of PLGN. They may provide novel therapies and a unique biomarker for diagnosis and monitoring class IV PLGN patients.