American Journal of Kidney Diseases
Volume 52, Issue 1 , Pages 171-180 , July 2008

Mutations in Proteins of the Alternative Pathway of Complement and the Pathogenesis of Atypical Hemolytic Uremic Syndrome

  • Cynthia Abarrategui-Garrido

      Affiliations

    • Research Unit, Hospital Universitario La Paz, Madrid, Spain
    • ,
  • Marta Melgosa, MD

      Affiliations

    • Pediatric Nephrology Unit, Hospital Universitario La Paz, Madrid, Spain
    • ,
  • Antonia Peña-Carrión, MD

      Affiliations

    • Pediatric Nephrology Unit, Hospital Universitario La Paz, Madrid, Spain
    • ,
  • Elena Goicoechea de Jorge, PhD

      Affiliations

    • Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain
    • ,
  • Santiago Rodríguez de Córdoba, PhD

      Affiliations

    • Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain
    • ,
  • Margarita López-Trascasa, PhD

      Affiliations

    • Immunology Unit. Hospital Universitario La Paz, Madrid, Spain.
    • ,
  • Pilar Sánchez-Corral, PhD

      Affiliations

    • Research Unit, Hospital Universitario La Paz, Madrid, Spain
    • Corresponding Author InformationAddress correspondence to Pilar Sánchez-Corral, PhD, Unidad de Investigación, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046-Madrid, Spain.

Received 4 June 2007 ,Accepted 2 January 2008.

References 

  1. Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol. 2005;16:1035–1050
  2. Pérez-Caballero D, González-Rubio C, Gallardo ME, et al. Clustering of missense mutations in the C-terminal region of factor H in atypical hemolytic uremic syndrome. Am J Hum Genet. 2001;68:478–484
  3. Richards A, Buddles MR, Donne RL, et al. Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition. Am J Hum Genet. 2001;68:485–490
  4. Caprioli J, Bettinaglio P, Zipfel PF, et al. The molecular basis of familial hemolytic uremic syndrome: Mutation analysis of factor H gene reveals a hot spot in short consensus repeat 20. J Am Soc Nephrol. 2001;12:297–307
  5. Neumann HPH, Salzmann M, Bohnert-Iwan B, et al. Haemolytic uraemic syndrome and mutations of the factor H gene: A registry-based study of German speaking countries. J Med Genet. 2003;40:676–681
  6. Dragon-Durey MA, Frémeaux-Bacchi V, Loirat C, et al. Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: Report and genetic analysis of 16 cases. J Am Soc Nephrol. 2004;15:787–795
  7. Richards A, Kemp EJ, Liszewski MK, et al. Mutations in human complement regulator, mebrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc Natl Acad Sci U S A. 2003;100:12966–12971
  8. Noris M, Brioschi S, Caprioli J, et al. Familial hemolytic uraemic syndrome and an MCP mutation. Lancet. 2003;362:1542–1547
  9. Frémeaux Bacchi V, Dragon-Durey MA, Blouin J, et al. Complement factor I: A susceptibility gene for atypical haemolytic uraemic syndrome. J Med Genet. 2004;41:e84
  10. Kavanagh D, Kemp EJ, Mayland E, et al. Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2005;16:2150–2155
  11. Esparza-Gordillo J, Goicoechea de Jorge E, Abarrategui-Garrido C, et al. Insights into hemolytic uremic syndrome: Segregation of three independent predisposition factors in a large, multiple affected pedigree. Mol Immunol. 2006;43:1769–1775
  12. Caprioli J, Castelletti F, Bucchioni S, et al. Complement factor H mutations and gene polymorphisms in hemolytic uremic syndrome: The c-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. Hum Mol Genet. 2003;12:3385–3395
  13. Esparza-Gordillo J, Goicoechea de Jorge E, López-Trascasa M, Sánchez-Corral P, Rodríguez de Córdoba S. Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32. Hum Mol Genet. 2005;14:703–712
  14. Fremeaux-Bacchi V, Kemp EJ, Goodship JA, et al. The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: Evidence from two independent cohorts. J Med Genet. 2005;42:852–856
  15. Dragon-Durey MA, Loirat C, Cloarec S, et al. Anti-factor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2005;16:555–563
  16. Zipfel PF, Edey M, Heinen S, et al. Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. PLoS Genetics. 2007;3:387–392
  17. Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. PNAS. 2007;104:240–245
  18. Fremeaux-Bacchi V, Goodship T, Regnier CH, Dragon-Furey MA, Janssen B, Atkinson J. Mutations in complement C3 predispose to development of atypical haemolytic uraemic syndrome. Mol Immunol. 2007;44:3923;(abstr)
  19. Caprioli J, Noris M, Brioschi S, et al. Genetics of HUS: The impact of MCP, CFH and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267–1279
  20. Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, et al. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2007;18:2392–2400
  21. Rodríguez de Córdoba S, Esparza-Gordillo J, Goicoechea de Jorge E, López-Trascasa M, Sánchez-Corral P. The human complement factor H: Functional roles, genetic variations and disease associations. Mol Immunol. 2004;41:355–367
  22. Saunders RE, Abarrategui-Garrido C, Frémeaux-Bacchi V, et al. The interactive factor H-atypical hemolytic uremic syndrome mutation database and website: Update and integration of membrane cofactor protein and factor I mutations with structural models. Hum Mutat. 2007;28:222–234
  23. Sánchez-Corral P, Pérez-Caballero D, Huarte O, et al. Structural and functional characterization of factor H mutations associated with atypical hemolytic uremic syndrome. Am J Hum Genet. 2002;71:1285–1295
  24. Manuelian T, Hellwage J, Meri S, et al. Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome. J Clin Invest. 2003;111:1181–1190
  25. Sánchez-Corral P, González-Rubio C, Rodríguez de Córdoba S, López-Trascasa M. Functional analysis in serum from atypical hemolytic uremic syndrome patients reveals impaired protection of host cells associated with mutations in factor H. Mol Immunol. 2004;41:81–84
  26. Vaziri-Sani F, Holmberg L, Sjöholm AG, et al. Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome. Kidney Int. 2006;69:981–988
  27. Besbas N, Karpman D, Landau D, et al. A classification of haemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int. 2006;70:423–431
  28. Jokiranta TS, Zipfel PF, Fremeaux-Bacchi V, Taylor CM, Goodship TJH, Noris M. Where next with atypical haemolytic uremic syndrome?. Mol Immunol. 2007;44:3889–3900
  29. Heinen S, Sanchez-Corral P, Jackson MS, et al. De novo gene conversion in the RCA gene cluster (1q32) causes mutations in complement factor H associated with atypical haemolytic uremic syndrome. Hum Mutat. 2006;27:292–293
  30. Jozsi M, Strobel S, Dahse HM, et al. Anti-factor H autoantibodies block C-terminal recognition function of factor H in haemolytic uremic syndrome. Blood. 2007;110:1516–1518
  31. Pickering MC, Goicoechea de Jorge E, Martínez-Barricarte R, et al. Spontaneous haemolytic uraemic syndrome triggered by complement factor H lacking surface recognition domains. J Exp Med. 2007;204:1249–1256
  32. Nathanson S, Frémeaux-Bacchi V, Deschênes G. Successful plasma therapy in hemolytic uremic syndrome with factor H deficiency. Pediatr Nephrol. 2001;16:554–556
  33. Licht C, Weyersberg A, Heinen S, et al. Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15. Am J Kidney Dis. 2005;45:415–421
  34. Nathanson S, Ulinski T, Frémeaux-Bacchi V, Deschênes G. Secondary failure of plasma therapy in factor H deficiency. Pediatr Nephrol. 2006;21:1769–1771
  35. Özçakar Z, Yalcinkaya F, Derelli E, et al. A favorable outcome of hemolytic uremic syndrome with factor H deficiency. Pediatr Nephrol. 2004;19:815–816
  36. Hahn H, Um EY, Park YS, Cheong HI. A case of atypical hemolytic uremic syndrome with a transient decrease in complement factor H. Pediatr Nephrol. 2006;21:295–298
  37. Stratton JD, Warwicker P. Successful treatment of factor H-related haemolytic uraemic syndrome. Nephrol Dial Transplant. 2002;17:684–685
  38. Gerber A, Kirchhoff-Moradpour AH, Obieglo S, et al. Successful (?) therapy of hemolytic-uremic syndrome with factor H abnormality. Pediatr Nephrol. 2003;18:952–955
  39. Filler G, Radhakrishnan S, Strain L, Hill A, Knoll G, Goodship TH. Challenges in the management of infantile factor H associated hemolytic uremic syndrome. Pediatr Nephrol. 2004;19:908–911
  40. Davin JC, Olie KH, Verlaak R, et al. Complement factor H-associated atypical hemolytic uremic syndrome in monozygotic twins: Concordant presentation, discordant response to treatment. Am J Kidney Dis. 2006;47:e27–e30

 Originally published online as doi:10.1053/j.ajkd.2008.01.026 on April 16, 2008.

PII: S0272-6386(08)00537-4

doi: 10.1053/j.ajkd.2008.01.026

American Journal of Kidney Diseases
Volume 52, Issue 1 , Pages 171-180 , July 2008

Article Tools

* Image Usage & Resolution