Dissecting IgA nephropathy via integration of multi-omics data

• Applicants: Professor Dr.-Ing. Julio Saez-Rodriguez; Dr. Claudia Seikrit, since 8/2023
• Subject Area: Nephrology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445703531

IgA Nephropathy (IgAN) is an immune-mediated disease characterized by accumulation of immunoglobulin A in the kidney, where it activates mesangial cells that proliferate, produce excess extracellular matrix and mount an inflammatory response that damages the kidney. These processes lead to kidney failure in about a third of patients. A much larger number develops Chronic Kidney Disease (CKD) that enormously increases the risk of cardiovascular disease. Recent GWAS studies and analyses of gene expression profiles point to a major role of various components of the immune system in IgAN, specially the complement system (whose components are often found in kidney biopsies of patients), and plasma B-cells. One key problem is that the human IgA is unique such that no animal models exist that allow to study early disease mechanisms of the human disease. Human studies are therefore key to dissect mechanistically how these components contribute to the pathophysiology of IgAN. Consequently, we propose a multi-omics characterization of kidney biopsies and blood of human patients from a carefully selected cohort of IgAN patients and controls from patients of other kidney conditions as well as healthy individuals. We will combine bulk and single-cell transcriptomics from biopsies and blood, peptidomics from blood and tissue proteomics via imaging mass spectrometry from biopsies. These –omics approaches will augment existing genetic, transcriptomics and peptidomic datasets. The data will be integrated using a combination of state-of-the-art computational approaches. The outcomes of this project will hopefully shed new light on the mechanisms underlying IgAN paving the way for developing novel biomarkers and therapies.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 5011: Integrating emerging methods to advance translational kidney research (InteraKD)
• Ehemaliger Antragsteller: Professor Dr. Jürgen Floege, until 7/2023