Three papers published almost simultaneously by the Centro de Investigaciones biológicas research group led by Prof. Rodríguez de Cordoba -two in Kidney Int. and one in J. Am. Soc. Nephrol.- identify novel genetic predisposition factors and environmental triggers for aHUS. Additionally, researchers propose a procedure for the categorization of genetic variants found in patients, which allows the identification of pathogenic variants.
In a retrospective study including 22 cases of pregnancy-associated aHUS, the authors show that 41% of the patients carry complement genetic abnormalities and associate the disease development to late pregnancy complications. Importantly, this study illustrates an excellent response of these aHUS patients to complement inhibition therapies.
In a second study, including 513 Spanish aHUS patients, they identified several patients carrying a novel genetic abnormality that involves transfer of DNA fragments between two complement genes. This genetic abnormality generates a strong competitor of factor H, the main complement regulator that prevents complement-mediated damage to host tissues, causing complement dysregulation and endothelial damage. The reported data illustrate the importance of performing comprehensive genetic studies and functional analysis to disclose pathogenic genetic abnormalities.
In this context, a third study describe an analytical strategy for the complete characterization of novel genetic variants identified in the genetic studies of patients and demonstrate its usefulness analyzing 28 novel disease-associated variants in factor H and categorizing 24 of them as pathogenic.
As a whole, their findings significantly improve prevention, diagnosis and treatment of aHUS patients.
Factor H Competitor Generated by Gene Conversion Events Associates with Atypical Hemolytic Uremic Syndrome. Goicoechea de Jorge E, Tortajada A, García SP, Gastoldi S, Merinero HM, García-Fernández J, Arjona E, Cao M, Remuzzi G, Noris M, Rodríguez de Córdoba S. J. Am. Soc. Nephrol. (2017). doi: 10.1681/ASN.2017050518
Complete functional characterization of disease-associated genetic variants in the complement factor H gene. Merinero HM, García SP, García-Fernández J, Arjona E, Tortajada A, Rodríguez de Córdoba S. Kidney Int. (2017). doi: 10.1016/j.kint.2017.07.015
A retrospective study of pregnancy-associated atypical hemolytic uremic syndrome. Huerta A, Arjona E, Portoles J, Lopez-Sanchez P, Rabasco C, Espinosa M, Cavero T, Blasco M, Cao M, Manrique J, Cabello-Chavez V, Suñer M, Heras M, Fulladosa X, Belmar L, Sempere A, Peralta C, Castillo L, Arnau A, Praga M, Rodríguez de Cordoba S. Kidney Int. (2017). doi: 10.1016/j.kint.2017.06.022