Role of factor H autoantibodies in hemolytic uremic syndrome and other kidney diseases

• Applicant: Dr. Mihály Józsi
• Subject Area: Nephrology
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 116161648

Hemolytic uremic syndrome is a severe kidney disease that manifests with thrombotic microangiopathy and acute renal failure. Its atypical form (aHUS) is often associated with mutations in genes encoding complement proteins. In addition, autoantibodies against complement factor H are present in some aHUS patients. The goal of the proposed project is to understand how autoantibodies cause this new, autoimmune form of aHUS. Purified autoantibodies will be used to study their effects on factor H functions, such as ligand binding and protection of cells from complement-mediated damage. Fine-mapping of binding epitopes on factor H and analysis of cross-reactivity with factor H-related proteins will provide further insights into the molecular basis of the disease. The pathological role of the autoantibodies will be assessed by monitoring the autoantibody titer, immune complexes and factor H activity during disease course and patient treatment. Samples will also be analyzed and characterized for new anti-complement autoantibodies. The results will give insights into the pathomechanism of aHUS and facilitate the development of specific treatment for this group of aHUS patients with factor H autoantibodies.

• DFG Programme: Research Grants