Complement Regulators

The effector function of the activated complement system on the surface of intact  autologous cells is tightly controlled and regulated. The Department of Infection Biology characterizes a family of human immune- and complement regulators termed Factor H Protein Family. This protein family with seven members includes Factor H as the central regulator, FHL1 which is encoded by an alternatively spliced transcript derived from the Factor H gene as well as five CFHR proteins (Complement Factor H related proteins) CFHR1 – CFHR5. CFHR represent unique innate immune regulators and the corresponding genes are positioned in a gene cluster which is located in close chromosomal proximity to the Factor H gene. Genetic variations in form of mutations, gene polymorphisms and copy number variations in the Factor H-CFHR1 gene cluster on the human chromosomes 1q32 are associated with several human diseases including the kidney disorders Hemolytic Uremic Syndrome (HUS) and Membranoproliferative Glomerulonephritis, (MPGN) also termed C3 glomerulopathy, as well as IgA Nephropathy, AMD (Age related macular degeneration ) a frequent form of blindness in elderly people of the western world and SLE (Systemic Lupus Erythematosus). Certain genetic scenarios like the common deletion of the CFHR3-CFHR1 genes occur in the healthy population and  have a protective role in AMD and IgA nephropathy but the same genetic constellation results confers risk for the autoimmune form of HUS and for SLE. For immune evasion of pathogenic fungi and microbes and in disease pathology, the functional characterization  of the infection is central for defining the understanding of the exact role of the individual proteins involved in the immune process. In addition, the interplay between the members of this protein family helps to define how these proteins switch and direct the immune and complement response.