Factor H-related proteins in the pathogenesis of atypical hemolytic-uremic syndrome

Atypical hemolytic-uremic syndrome (aHUS) is a rare disease of the group of thrombotic microangiopathies caused by hyperactivation of an alternative pathway of the complement system. One of the mechanisms of aHUS development is the change in the functional activity of proteins of the factor H (FH) family. We analyzed the available data on the influence of factor H protein family on aHUS development. A total of 43 studies published in 2003-2021, including 41 foreign ones, were reviewed. PubMed, Web of Science, Scopus, еLibrary, Google Scholar databases were searched using keywords: aHUS, factor H, factor H-like protein, factor H-related proteins (FHRs). Priority was given to the results of randomized controlled trials, systematic reviews with meta-analysis. Duplicate articles were excluded. Based on the analysis results, conclusions were drawn that disruption of C3b subunit inactivation as a result of changes in the functional activity of FH family proteins mediates the formation of a membrane-attacking complex. Among the mechanisms of FH, FHR1, and FHR3 inhibition are genetic aberrations (missense mutations, reading frame shift), formation of hybrid proteins, and synthesis of autologous antibodies. Other mechanisms of alternative pathway hyperactivation include decreased concentration or complete absence of FH, FHR1, FHR3, and FHR4 as a result of deletion of 1q31.3 fragments or formation of hybrid proteins. The change in the FH functional activity is also possible due to autoinactivation or competitive inhibition when the FHRs concentration increases.