POS-407 COMPLEMENT RECEPTOR 1 IS A POTENTIAL THERAPEUTIC TARGET OF INTERSTITIAL LESION IN IgA NEPHROPATHY

Abstract

IgA nephropathy is one of leading causes of chronic kidney disease. Interstitial lesion in IgA nephropathy is correlated with unfavorable prognosis. Sensitive biomarkers are important for early detection and intervention targets of the disease. This study aims to identify Complement Receptor 1 (CR1) as a potential therapeutic target in IgA nephropathy patients with interstitial lesion. Renal tissue proteomics data is accessed from a local IgA nephropathy cohort with 59 IgA nephropathy patients and 19 healthy controls. CD21/35+B cells are separated with fluorescence activated cell sorting from mice spleen. Adaptive transfer is operated with a single injection from the renal vein immediately after urethral obstruction. Renal pathology is evaluated on pictures captured by a visual microscope. CR1 is identified as the most significantly downregulated complement component in IgA nephropathy patients. Clinical information characterization of IgA nephropathy patients is assessed with Pearson R correlation test to confirm their linear independence. Of the 28 complement components recognized, 24 protein expression is increased in IgA nephropathy patients and 4 is decreased compared to healthy control. CR1 is identified as the most significantly decreased complement component in IgA nephropathy patients. CR1 protein expression is inversely correlated with IgA nephropathy interstitial lesion but not with renal function progress. Further correlation analysis of clinical information reveals that CR1 protein expression is inversely correlated with IgA nephropathy interstitial lesion, as represented as Oxford Classification T score. However, CR1 is not significantly correlated with serum creatine level or renal function loss progress (calculated as average eGFR decline per month). CD21/35+ cells are increased in the experimental renal interstitial injury mice. To test the hypothesis CR1 may be associated with interstitial lesion, we study the CD21/35 (CD21/35 is the mouse homolog of CR1 molecule) expression in unilateral urethral obstruction mice. We find that CD45+bone marrow derived cells significantly infiltrated the obstructed kidney at day 12, of which the CD5+ CD21/35+cells significantly increased compared to control. Adaptive transfer of CD21/35+B cells protects the cortex structure in experimental renal interstitial injury. To test whether the CD21/35 molecule on immune cells are protective against interstitial lesion, we sorted CD21/35+B cells and CD21/35-B cells and test their respective protective potential through adaptive transfer into UUO mice. We find that the renal cortex width is significantly increased in CD21/35+group than that in CD21/35-group at day 12 after UUO. CR1 is inversely correlated with renal interstitial lesion in IgA nephropathy patients and is potentially protective in experimental renal interstitial injury.