Genetics and complement in atypical HUS

Pediatric Nephrology

Volumn 25, Issue 12, 2010, Pages 2431-2442

  Kavanagh, David ^a   Goodship, Tim ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Complement; Factor H; Factor I; Hemolytic uremic syndrome; Membrane cofactor protein; Thrombomodulin; Thrombotic thrombocytopenic purpura; Transplantation

Indexed keywords

ALTERNATIVE COMPLEMENT PATHWAY C3 C5 CONVERTASE; AUTOANTIBODY; COMPLEMENT COMPONENT C3; COMPLEMENT FACTOR H; COMPLEMENT FACTOR H AUTOANTIBODY; COMPLEMENT FACTOR I; MEMBRANE COFACTOR PROTEIN; THROMBOMODULIN; UNCLASSIFIED DRUG;

ATYPICAL HEMOLYTIC UREMIC SYNDROME; GENE MUTATION; GENETICS; GENOTYPE; HEMOLYTIC UREMIC SYNDROME; HUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW;

AUTOANTIBODIES; COMPLEMENT ACTIVATION; COMPLEMENT SYSTEM PROTEINS; GENETIC PREDISPOSITION TO DISEASE; HEMOLYTIC-UREMIC SYNDROME; HUMANS; MUTATION; PENETRANCE; PHENOTYPE; RISK ASSESSMENT; RISK FACTORS;

EID: 78449293078     PISSN: 0931041X     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00467-010-1555-5     Document Type: Review

References (90)

1. D Kavanagh A Richards J Atkinson 2008 Complement regulatory genes and hemolytic uremic syndromes Annu Rev Med 59 293 309 1:CAS:528: DC%2BD1cXis12nuro%3D 10.1146/annurev.med.59.060106.185110 17705684
2. Fogo A, Kashgarian M (2005) Diagnostic atlas of renal pathology. Elsevier Science, Amsterdam
3. PI Tarr CA Gordon WL Chandler 2005 Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome Lancet 365 1073 1086 1:CAS:528: DC%2BD2MXisFGrs7Y%3D 15781103
4. M Noris G Remuzzi 2005 Hemolytic uremic syndrome J Am Soc Nephrol 16 1035 1050 1:CAS:528:DC%2BD2MXjsVGgu7o%3D 10.1681/ASN.2004100861 15728781
5. G Ariceta N Besbas S Johnson D Karpman D Landau C Licht C Loirat C Pecoraro CM Taylor N Van de Kar J Vandewalle LB Zimmerhackl 2009 Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome Pediatr Nephrol 24 687 696 10.1007/s00467-008-0964-1 18800230
6. S Rodriguez de Cordoba J Esparza-Gordillo E Goicoechea de Jorge M Lopez-Trascasa P Sanchez-Corral 2004 The human complement factor H: functional roles, genetic variations and disease associations Mol Immunol 41 355 367 1:CAS:528:DC%2BD2cXktFKksrs%3D 10.1016/j.molimm.2004.02.005 15163532
7. A Richards D Kavanagh JP Atkinson 2007 Inherited complement regulatory protein deficiency predisposes to human disease in acute injury and chronic inflammatory states: the examples of vascular damage in atypical hemolytic uremic syndrome and debris accumulation in age-related macular degeneration Adv Immunol 96 141 177 1:CAS:528:DC%2BD1cXhs1ajtbY%3D 10.1016/S0065-2776(07)96004-6 17981206
8. HG Hocking AP Herbert D Kavanagh DC Soares VP Ferreira MK Pangburn D Uhrin PN Barlow 2008 Structure of the N-terminal region of complement factor H and conformational implications of disease-linked sequence variations J Biol Chem 283 9475 9487 1:CAS:528:DC%2BD1cXjslyqsb0%3D 10.1074/jbc.M709587200 18252712
9. CQ Schmidt AP Herbert D Kavanagh C Gandy CJ Fenton BS Blaum M Lyon D Uhrin PN Barlow 2008 A new map of glycosaminoglycan and C3b binding sites on factor H J Immunol 181 2610 2619 1:CAS:528:DC%2BD1cXptlOjsrw%3D 18684951
10. P Warwicker TH Goodship RL Donne Y Pirson A Nicholls RM Ward P Turnpenny JA Goodship 1998 Genetic studies into inherited and sporadic hemolytic uremic syndrome Kidney Int 53 836 844 1:CAS:528:DyaK1cXisVKmsb0%3D 10.1111/j.1523-1755. 1998.00824.x 9551389
11. A Richards MR Buddles RL Donne BS Kaplan E Kirk MC Venning CL Tielemans JA Goodship TH Goodship 2001 Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition Am J Hum Genet 68 485 490 1:CAS:528:DC%2BD3MXhtl2lsLY%3D 10.1086/318203 11170896
12. MA Dragon-Durey V Fremeaux-Bacchi C Loirat J Blouin P Niaudet G Deschenes P Coppo W Herman Fridman L Weiss 2004 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 15 787 795 1:CAS:528:DC%2BD2cXhtlShu7w%3D 10.1097/01.ASN.0000115702.28859.A7 14978182
13. J Caprioli M Noris S Brioschi G Pianetti F Castelletti P Bettinaglio C Mele E Bresin L Cassis S Gamba F Porrati S Bucchioni G Monteferrante CJ Fang MK Liszewski D Kavanagh JP Atkinson G Remuzzi 2006 Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome Blood 108 1267 1279 1:CAS:528:DC%2BD28Xot1ymtbk%3D 10.1182/blood-2005- 10-007252 16621965
14. HP Neumann M Salzmann B Bohnert-Iwan T Mannuelian C Skerka D Lenk BU Bender M Cybulla P Riegler A Konigsrainer U Neyer A Bock U Widmer DA Male G Franke PF Zipfel 2003 Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German-speaking countries J Med Genet 40 676 681 1:CAS:528:DC%2BD3sXot1yitLw%3D 10.1136/jmg.40.9.676 12960213
15. D Perez-Caballero C Gonzalez-Rubio ME Gallardo M Vera M Lopez-Trascasa S Rodriguez de Cordoba P Sanchez-Corral 2001 Clustering of missense mutations in the C-terminal region of factor H in atypical hemolytic uremic syndrome Am J Hum Genet 68 478 484 1:CAS:528:DC%2BD3MXhtl2lsLk%3D 10.1086/318201 11170895
16. D Westra E Volokhina E van der Heijden A Vos M Huigen J Jansen E van Kaauwen T van der Velden N van de Kar L van den Heuvel 2010 Genetic disorders in complement (regulating) genes in patients with atypical haemolytic uraemic syndrome (aHUS) Nephrol Dial Transplant 10.1093/ndt/gfq010 20106822
17. S Heinen P Sanchez-Corral MS Jackson L Strain JA Goodship EJ Kemp C Skerka TS Jokiranta K Meyers E Wagner P Robitaille J Esparza-Gordillo S Rodriguez de Cordoba PF Zipfel TH Goodship 2006 De novo gene conversion in the RCA gene cluster (1q32) causes mutations in complement factor H associated with atypical hemolytic uremic syndrome Hum Mutat 27 292 293 10.1002/humu.9408 16470555
18. JP Venables L Strain D Routledge D Bourn HM Powell P Warwicker ML Diaz-Torres A Sampson P Mead M Webb Y Pirson MS Jackson A Hughes KM Wood JA Goodship TH Goodship 2006 Atypical haemolytic uraemic syndrome associated with a hybrid complement gene PLoS Med 3 e431 10.1371/journal.pmed.0030431 17076561
19. VP Ferreira AP Herbert C Cortes KA McKee BS Blaum ST Esswein D Uhrin PN Barlow MK Pangburn D Kavanagh 2009 The binding of factor H to a complex of physiological polyanions and C3b on cells is impaired in atypical hemolytic uremic syndrome J Immunol 182 7009 7018 1:CAS:528:DC%2BD1MXmtVKqsb4%3D 10.4049/jimmunol.0804031 19454698
20. P Sanchez-Corral C Gonzalez-Rubio S Rodriguez de Cordoba M Lopez-Trascasa 2004 Functional analysis in serum from atypical hemolytic uremic syndrome patients reveals impaired protection of host cells associated with mutations in factor H Mol Immunol 41 81 84 1:CAS:528:DC%2BD2cXjvFKqu7s%3D 10.1016/j.molimm.2004.01.003 15140578
21. C Abarrategui-Garrido M Melgosa A Pena-Carrion EG de Jorge SR de Cordoba M Lopez-Trascasa P Sanchez-Corral 2008 Mutations in proteins of the alternative pathway of complement and the pathogenesis of atypical hemolytic uremic syndrome Am J Kidney Dis 52 171 180 1:CAS:528:DC%2BD1cXpt1eis7g%3D 10.1053/j.ajkd.2008. 01.026 18423815
22. F Vaziri-Sani L Holmberg AG Sjoholm AC Kristoffersson M Manea V Fremeaux-Bacchi I Fehrman-Ekholm R Raafat D Karpman 2006 Phenotypic expression of factor H mutations in patients with atypical hemolytic uremic syndrome Kidney Int 69 981 988 1:CAS:528:DC%2BD28XitFGht7c%3D 10.1038/sj.ki.5000155 16528247
23. AL Stahl F Vaziri-Sani S Heinen AC Kristoffersson KH Gydell R Raafat A Gutierrez O Beringer PF Zipfel D Karpman 2008 Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation Blood 111 5307 5315 10.1182/blood-2007-08-106153 18268093
24. S Heinen M Jozsi A Hartmann M Noris G Remuzzi C Skerka PF Zipfel 2007 Hemolytic uremic syndrome: a factor H mutation (E1172Stop) causes defective complement control at the surface of endothelial cells J Am Soc Nephrol 18 506 514 1:CAS:528:DC%2BD2sXit12ju78%3D 10.1681/ASN.2006091069 17229916
25. R Nan J Gor SJ Perkins 2008 Implications of the progressive self-association of wild-type human factor H for complement regulation and disease J Mol Biol 375 891 900 1:CAS:528:DC%2BD1cXhtlGrsA%3D%3D 10.1016/j.jmb.2007.11.015 18054958
26. MK Pangburn N Rawal C Cortes MN Alam VP Ferreira MA Atkinson 2009 Polyanion-induced self-association of complement factor H J Immunol 182 1061 1068 1:CAS:528:DC%2BD1MXhsVKluw%3D%3D 19124749
27. AI Okemefuna K Li R Nan RJ Ormsby T Sadlon DL Gordon SJ Perkins 2009 Multimeric interactions between complement factor H and its C3d ligand provide new insight on complement regulation J Mol Biol 391 119 135 1:CAS:528: DC%2BD1MXoslantr0%3D 10.1016/j.jmb.2009.06.013 19505474
28. A Richards D Kavanagh 2009 Pathogenesis of thrombotic microangiopathy: insights from animal models Nephron Exp Nephrol 113 e97 e103 10.1159/000235253 19684414
29. MC Pickering HT Cook J Warren AE Bygrave J Moss MJ Walport M Botto 2002 Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H Nat Genet 31 424 428 1:CAS:528: DC%2BD38Xls1Orsr0%3D 12091909
30. GA Hegasy T Manuelian K Hogasen JH Jansen PF Zipfel 2002 The molecular basis for hereditary porcine membranoproliferative glomerulonephritis type II: point mutations in the factor H coding sequence block protein secretion Am J Pathol 161 2027 2034 1:CAS:528:DC%2BD38Xpslemur4%3D 12466119
31. MC Pickering EG de Jorge R Martinez-Barricarte S Recalde A Garcia-Layana KL Rose J Moss MJ Walport HT Cook SR de Cordoba M Botto 2007 Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains J Exp Med 204 1249 1256 1:CAS:528:DC%2BD2sXms1aktro%3D 10.1084/jem.20070301 17517971
32. E Goicoechea de Jorge D Paixao-Cavalcante K Rose H Cook M Botto M Pickering 2008 C5 activation is required for the development of atypical haemolytic uraemic syndrome in Cfh-/-FH Delta 16-20 mice Mol Immunol 44 4100
33. A Richards M Kathryn Liszewski D Kavanagh CJ Fang E Moulton V Fremeaux-Bacchi G Remuzzi M Noris TH Goodship JP Atkinson 2007 Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome Mol Immunol 44 111 122 1:CAS:528: DC%2BD28XhtFartLnI 10.1016/j.molimm.2006.07.004 16882452
34. A Richards EJ Kemp MK Liszewski JA Goodship AK Lampe R Decorte MH Muslumanoglu S Kavukcu G Filler Y Pirson LS Wen JP Atkinson TH Goodship 2003 Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome Proc Natl Acad Sci USA 100 12966 12971 1:CAS:528:DC%2BD3sXoslKmsrs%3D 10.1073/pnas.2135497100 14566051
35. V Fremeaux-Bacchi EA Moulton D Kavanagh MA Dragon-Durey J Blouin A Caudy N Arzouk R Cleper M Francois G Guest J Pourrat R Seligman WH Fridman C Loirat JP Atkinson 2006 Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome J Am Soc Nephrol 17 2017 2025 1:CAS:528:DC%2BD28Xntlanu7w%3D 10.1681/ASN.2005101051 16762990
36. M Noris S Brioschi J Caprioli M Todeschini E Bresin F Porrati S Gamba G Remuzzi 2003 Familial haemolytic uraemic syndrome and an MCP mutation Lancet 362 1542 1547 1:CAS:528:DC%2BD3sXovVWlsrs%3D 10.1016/S0140-6736(03)14742-3 14615110
37. M Sullivan Z Erlic MM Hoffmann K Arbeiter L Patzer K Budde B Hoppe M Zeier K Lhotta LA Rybicki A Bock G Berisha HP Neumann 2010 Epidemiological approach to identifying genetic predispositions for atypical hemolytic uremic syndrome Ann Hum Genet 74 17 26 1:CAS:528:DC%2BC3cXht1OmtLw%3D 10.1111/j.1469-1809.2009.00554.x 20059470
38. CJ Fang V Fremeaux-Bacchi MK Liszewski G Pianetti M Noris TH Goodship JP Atkinson 2008 Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome Blood 111 624 632 1:CAS:528:DC%2BD1cXns1CnsQ%3D%3D 10.1182/blood-2007-04-084533 17914026
39. MK Pangburn RD Schreiber HJ Muller-Eberhard 1977 Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein beta1H for cleavage of C3b and C4b in solution J Exp Med 146 257 270 1:CAS:528:DyaE2sXltVSntro%3D 10.1084/jem.146.1.257 301546
40. K Whaley S Ruddy 1976 Modulation of C3b hemolytic activity by a plasma protein distinct from C3b inactivator Science 193 1011 1013 1:CAS:528: DyaE28XlsVWhsLg%3D 10.1126/science.948757 948757
41. S Nagasawa RM Stroud 1977 Mechanism of action of the C3b inactivator: requirement for a high molecular weight cofactor (C3b-C4bINA cofactor) and production of a new C3b derivative (C3b′) Immunochemistry 14 749 756 1:CAS:528:DyaE1cXhtlCltrs%3D 10.1016/0019-2791(77)90345-7 146022
42. S Shiraishi RM Stroud 1975 Cleavage products of C4b produced by enzymes in human serum Immunochemistry 12 935 939 1:CAS:528:DyaE28XhtVekt70%3D 10.1016/0019-2791(75)90256-6 815169
43. MK Liszewski TW Post JP Atkinson 1991 Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster Annu Rev Immunol 9 431 455 1:CAS:528:DyaK3MXmsFegurk%3D 10.1146/annurev.iy.09. 040191.002243 1910685
44. ME Medof K Iida C Mold V Nussenzweig 1982 Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes J Exp Med 156 1739 1754 1:CAS:528:DyaL3sXoslertQ%3D%3D 10.1084/jem.156.6.1739 7175439
45. GD Ross JD Lambris JA Cain SL Newman 1982 Generation of three different fragments of bound C3 with purified factor I or serum. I. Requirements for factor H vs. CR1 cofactor activity J Immunol 129 2051 2060 1:CAS:528: DyaL38XmtFequ7g%3D 6214588
46. D Kavanagh EJ Kemp E Mayland RJ Winney JS Duffield G Warwick A Richards R Ward JA Goodship TH Goodship 2005 Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome J Am Soc Nephrol 16 2150 2155 1:CAS:528:DC%2BD2MXms1egsL4%3D 10.1681/ASN.2005010103 15917334
47. D Kavanagh A Richards M Noris R Hauhart MK Liszewski D Karpman JA Goodship V Fremeaux-Bacchi G Remuzzi TH Goodship JP Atkinson 2008 Characterization of mutations in complement factor I (CFI) associated with hemolytic uremic syndrome Mol Immunol 45 95 105 1:CAS:528:DC%2BD2sXpsl2hsbk%3D 10.1016/j.molimm.2007.05.004 17597211
48. V Fremeaux-Bacchi MA Dragon-Durey J Blouin C Vigneau D Kuypers B Boudailliez C Loirat E Rondeau WH Fridman 2004 Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome J Med Genet 41 e84 1:STN:280:DC%2BD2czgvFyjug%3D%3D 10.1136/jmg.2004.019083 15173250
49. AL Sellier-Leclerc V Fremeaux-Bacchi MA Dragon-Durey MA Macher P Niaudet G Guest B Boudailliez F Bouissou G Deschenes S Gie M Tsimaratos M Fischbach D Morin H Nivet C Alberti C Loirat 2007 Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome J Am Soc Nephrol 18 2392 2400 1:CAS:528:DC%2BD2sXpslers7o%3D 10.1681/ASN.2006080811 17599974
50. F Bienaime MA Dragon-Durey CH Regnier SC Nilsson WH Kwan J Blouin M Jablonski N Renault MA Rameix-Welti C Loirat C Sautes-Fridman BO Villoutreix AM Blom V Fremeaux-Bacchi 2010 Mutations in components of complement influence the outcome of factor I-associated atypical hemolytic uremic syndrome Kidney Int 77 339 349 1:CAS:528:DC%2BC3cXht1Kksrg%3D 10.1038/ki.2009.472 20016463
51. PF de Paula JE Barbosa PR Junior VP Ferriani MR Latorre V Nudelman L Isaac 2003 Ontogeny of complement regulatory proteins-concentrations of factor h, factor I, c4b-binding protein, properdin and vitronectin in healthy children of different ages and in adults Scand J Immunol 58 572 577 10.1046/j.1365-3083. 2003.01326.x 14629629
52. SC Nilsson N Kalchishkova LA Trouw V Fremeaux-Bacchi BO Villoutreix AM Blom 2010 Mutations in complement factor I as found in atypical hemolytic uremic syndrome lead to either altered secretion or altered function of factor I Eur J Immunol 40 172 185 1:CAS:528:DC%2BC3cXktVKi 10.1002/eji.200939280 19877009
53. SC Nilsson D Karpman F Vaziri-Sani AC Kristoffersson R Salomon F Provot V Fremeaux-Bacchi LA Trouw AM Blom 2007 A mutation in factor I that is associated with atypical hemolytic uremic syndrome does not affect the function of factor I in complement regulation Mol Immunol 44 1835 1844 1:CAS:528:DC%2BD28Xht1KitbzM 10.1016/j.molimm.2006.10.005 17084897
54. H Weiler BH Isermann 2003 Thrombomodulin J Thromb Haemost 1 1515 1524 1:CAS:528:DC%2BD2cXktFOjtr8%3D 10.1046/j.1538-7836.2003.00306.x 12871287
55. M Delvaeye M Noris A De Vriese CT Esmon NL Esmon G Ferrell J Del-Favero S Plaisance B Claes D Lambrechts C Zoja G Remuzzi EM Conway 2009 Thrombomodulin mutations in atypical hemolytic-uremic syndrome N Engl J Med 361 345 357 1:CAS:528:DC%2BD1MXovFCrs78%3D 10.1056/NEJMoa0810739 19625716
56. E Goicoechea de Jorge CL Harris J Esparza-Gordillo L Carreras EA Arranz CA Garrido M Lopez-Trascasa P Sanchez-Corral BP Morgan S Rodriguez de Cordoba 2007 Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome Proc Natl Acad Sci USA 104 240 245 1:CAS:528:DC%2BD2sXjt1Ohsg%3D%3D 10.1073/pnas.0603420103 17182750
57. D Kavanagh EJ Kemp A Richards RM Burgess E Mayland JA Goodship TH Goodship 2006 Does complement factor B have a role in the pathogenesis of atypical HUS? Mol Immunol 43 856 859 1:CAS:528:DC%2BD2MXhtlertL7E 10.1016/j.molimm.2005.06.041 16061287
58. LT Roumenina M Jablonski C Hue J Blouin JD Dimitrov MA Dragon-Durey M Cayla WH Fridman MA Macher D Ribes L Moulonguet L Rostaing SC Satchell PW Mathieson C Sautes-Fridman C Loirat CH Regnier L Halbwachs-Mecarelli V Fremeaux-Bacchi 2009 Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome Blood 114 2837 2845 1:CAS:528:DC%2BD1MXht1eit7nJ 19584399
59. K Lhotta AR Janecke J Scheiring B Petzlberger T Giner V Fally R Wurzner LB Zimmerhackl G Mayer V Fremeaux-Bacchi 2009 A large family with a gain-of-function mutation of complement C3 predisposing to atypical hemolytic uremic syndrome, microhematuria, hypertension and chronic renal failure Clin J Am Soc Nephrol 4 1356 1362 1:CAS:528:DC%2BD1MXhtV2qur3E 10.2215/CJN.06281208 19590060
60. V Fremeaux-Bacchi EC Miller MK Liszewski L Strain J Blouin AL Brown N Moghal BS Kaplan RA Weiss K Lhotta G Kapur T Mattoo H Nivet W Wong S Gie BH de Ligny M Fischbach R Gupta R Hauhart V Meunier C Loirat MA Dragon-Durey WH Fridman BJ Janssen TH Goodship JP Atkinson 2008 Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome Blood 112 4948 4952 1:CAS:528:DC%2BD1cXhsFWms7zF 10.1182/blood-2008-01-133702 18796626
61. I Moore L Strain I Pappworth D Kavanagh PN Barlow AP Herbert CQ Schmidt S Staniforth L Holmes R Ward L Morgan TH Goodship K Marchbank 2010 Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4 and with mutations in CFH, CFI, CD46 and C3 in patients with atypical haemolytic uraemic syndrome Blood 10.1182/blood-2009-05-221549
62. C Abarrategui-Garrido R Martinez-Barricarte M Lopez-Trascasa S Rodriguez de Cordoba P Sanchez-Corral 2009 Characterization of complement factor H-related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome Blood 114 4261 4271 1:CAS:528: DC%2BD1MXhsVGku7jE 10.1182/blood-2009-05-223834 19745068
63. MA Dragon-Durey C Loirat S Cloarec MA Macher J Blouin H Nivet L Weiss WH Fridman V Fremeaux-Bacchi 2005 Anti-Factor H autoantibodies associated with atypical hemolytic uremic syndrome J Am Soc Nephrol 16 555 563 1:CAS:528:DC%2BD2MXhvVCkt7g%3D 10.1681/ASN.2004050380 15590760
64. M Jozsi C Licht S Strobel SL Zipfel H Richter S Heinen PF Zipfel C Skerka 2008 Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency Blood 111 1512 1514 1:CAS:528:DC%2BD1cXhvFejurY%3D 10.1182/blood-2007-09-109876 18006700
65. M Jozsi S Strobel HM Dahse WS Liu PF Hoyer M Oppermann C Skerka PF Zipfel 2007 Anti factor H autoantibodies block C-terminal recognition function of factor H in hemolytic uremic syndrome Blood 110 1516 1518 1:CAS:528: DC%2BD2sXhtVSgsb3P 10.1182/blood-2007-02-071472 17495132
66. PF Zipfel M Edey S Heinen M Jozsi H Richter J Misselwitz B Hoppe D Routledge L Strain AE Hughes JA Goodship C Licht TH Goodship C Skerka 2007 Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome PLoS Genet 3 e41 10.1371/journal.pgen. 0030041 17367211
67. AL Stahl A Kristoffersson AI Olin ML Olsson AM Roodhooft W Proesmans D Karpman 2009 A novel mutation in the complement regulator clusterin in recurrent hemolytic uremic syndrome Mol Immunol 46 2236 2243 1:CAS:528: DC%2BD1MXntFynsrc%3D 10.1016/j.molimm.2009.04.012 19446882
68. DE Jenne J Tschopp 1992 Clusterin: the intriguing guises of a widely expressed glycoprotein Trends Biochem Sci 17 154 159 1:CAS:528: DyaK38XitlShur0%3D 10.1016/0968-0004(92)90325-4 1585460
69. J Tschopp DE Jenne S Hertig KT Preissner H Morgenstern AP Sapino L French 1993 Human megakaryocytes express clusterin and package it without apolipoprotein A-1 into alpha-granules Blood 82 118 125 1:CAS:528: DyaK3sXltFCht7o%3D 8324215
70. S Rodriguez de Cordoba 2010 aHUS: a disorder with many risk factors Blood 115 158 160 1:CAS:528:DC%2BC3cXhtlKlsrc%3D 10.1182/blood-2009-11-252627 20075170
71. D Kavanagh R Burgess D Spitzer A Richards ML Diaz-Torres JA Goodship DE Hourcade JP Atkinson TH Goodship 2007 The decay accelerating factor mutation I197V found in hemolytic uraemic syndrome does not impair complement regulation Mol Immunol 44 3162 3167 1:CAS:528:DC%2BD2sXksVeisrs%3D 10.1016/j.molimm.2007. 01.036 17368771
72. G Monteferrante S Brioschi J Caprioli G Pianetti P Bettinaglio E Bresin G Remuzzi M Noris 2007 Genetic analysis of the complement factor H-related 5 gene in haemolytic uraemic syndrome Mol Immunol 44 1704 1708 1:CAS:528: DC%2BD28Xht1ems7nN 10.1016/j.molimm.2006.08.004 17000000
73. V Fremeaux-Bacchi EJ Kemp JA Goodship MA Dragon-Durey L Strain C Loirat HW Deng TH Goodship 2005 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 42 852 856 1:CAS:528:DC%2BD2MXht1KrtbbE 10.1136/jmg.2005.030783 15784724
74. J Esparza-Gordillo E Goicoechea de Jorge A Buil L Carreras Berges M Lopez-Trascasa P Sanchez-Corral S Rodriguez de Cordoba 2005 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 14 703 712 1:CAS:528:DC%2BD2MXhsFSgsLg%3D 10.1093/hmg/ddi066 15661753
75. J Esparza-Gordillo EG Jorge CA Garrido L Carreras M Lopez-Trascasa P Sanchez-Corral SR de Cordoba 2006 Insights into hemolytic uremic syndrome: segregation of three independent predisposition factors in a large, multiple affected pedigree Mol Immunol 43 1769 1775 1:CAS:528:DC%2BD28XisFers7k%3D 10.1016/j.molimm.2005.11.008 16386793
76. R Martinez-Barricarte G Pianetti R Gautard J Misselwitz L Strain V Fremeaux-Bacchi C Skerka PF Zipfel T Goodship M Noris G Remuzzi SR de Cordoba 2008 The complement factor H R1210C mutation is associated with atypical hemolytic uremic syndrome J Am Soc Nephrol 19 639 646 1:CAS:528: DC%2BD1cXktVamt7k%3D 10.1681/ASN.2007080923 18235085
77. AM Blom F Bergstrom M Edey M Diaz-Torres D Kavanagh A Lampe JA Goodship L Strain N Moghal M McHugh C Inward C Tomson V Fremeaux-Bacchi BO Villoutreix TH Goodship 2008 A novel non-synonymous polymorphism (p.Arg240His) in C4b-binding protein is associated with atypical hemolytic uremic syndrome and leads to impaired alternative pathway cofactor activity J Immunol 180 6385 6391 1:CAS:528:DC%2BD1cXkvVCjtL0%3D 18424762
78. A Tortajada T Montes R Martinez-Barricarte BP Morgan CL Harris SR de Cordoba 2009 The disease-protective complement factor H allotypic variant Ile62 shows increased binding affinity for C3b and enhanced cofactor activity Hum Mol Genet 18 3452 3461 1:CAS:528:DC%2BD1MXhtVehurfI 10.1093/hmg/ddp289 19549636
79. J Scharfstein A Ferreira I Gigli V Nussenzweig 1978 Human C4-binding protein. I. Isolation and characterization J Exp Med 148 207 222 1:CAS:528:DyaE1cXlt1CktLg%3D 10.1084/jem.148.1.207 670886
80. T Fujita I Gigli V Nussenzweig 1978 Human C4-binding protein. II. Role in proteolysis of C4b by C3b-inactivator J Exp Med 148 1044 1051 1:CAS:528:DyaE1MXjslGitg%3D%3D 10.1084/jem.148.4.1044 702059
81. R Martinez-Barricarte E Goicoechea de Jorge T Montes AG Layana S Rodriguez de Cordoba 2009 Lack of association between polymorphisms in C4b-binding protein and atypical haemolytic uraemic syndrome in the Spanish population Clin Exp Immunol 155 59 64 1:CAS:528:DC%2BD1MXhsFCgtLs%3D 10.1111/j.1365-2249.2008.03798.x 19076829
82. D Kavanagh TH Goodship A Richards 2006 Atypical haemolytic uraemic syndrome Br Med Bull 77-78 5 22 10.1093/bmb/ldl004 16968692
83. C Loirat V Fremeaux-Bacchi 2008 Hemolytic uremic syndrome recurrence after renal transplantation Pediatr Transplant 12 619 629 1:CAS:528: DC%2BD1cXhtFSltbvM 10.1111/j.1399-3046.2008.00910.x 18482212
84. Kavanagh D, Richards A, Goodship TH, Jalanko H (2010) Transplantation in atypical hemolytic uremic syndrome. Semin Thromb Hemost. doi
85. E Bresin E Daina M Noris F Castelletti R Stefanov P Hill TH Goodship G Remuzzi 2006 Outcome of renal transplantation in patients with non-Shiga toxin-associated hemolytic uremic syndrome: prognostic significance of genetic background Clin J Am Soc Nephrol 1 88 99 1:CAS:528:DC%2BD28XjvV2gsr0%3D 10.2215/CJN.00050505 17699195
86. MJ Lehtinen AL Rops DE Isenman J van der Vlag TS Jokiranta 2009 Mutations of factor H impair regulation of surface-bound C3b by three mechanisms in atypical hemolytic uremic syndrome J Biol Chem 284 15650 15658 1:CAS:528:DC%2BD1MXmsFyqtLc%3D 10.1074/jbc.M900814200 19351878
87. M Jozsi S Heinen A Hartmann CW Ostrowicz S Halbich H Richter A Kunert C Licht RE Saunders SJ Perkins PF Zipfel C Skerka 2006 Factor H and atypical hemolytic uremic syndrome: mutations in the C-terminus cause structural changes and defective recognition functions J Am Soc Nephrol 17 170 177 1:CAS:528:DC%2BD28XhtFyqu7o%3D 10.1681/ASN.2005080868 16338962
88. TS Jokiranta ZZ Cheng H Seeberger M Jozsi S Heinen M Noris G Remuzzi R Ormsby DL Gordon S Meri J Hellwage PF Zipfel 2005 Binding of complement factor H to endothelial cells is mediated by the carboxy-terminal glycosaminoglycan binding site Am J Pathol 167 1173 1181 1:CAS:528:DC%2BD2MXhtFKqtLfJ 16192651
89. T Manuelian J Hellwage S Meri J Caprioli M Noris S Heinen M Jozsi HP Neumann G Remuzzi PF Zipfel 2003 Mutations in factor H reduce binding affinity to C3b and heparin and surface attachment to endothelial cells in hemolytic uremic syndrome J Clin Invest 111 1181 1190 1:CAS:528:DC%2BD3sXjtFCrs7w%3D 12697737
90. P Sanchez-Corral D Perez-Caballero O Huarte AM Simckes E Goicoechea M Lopez-Trascasa SR de Cordoba 2002 Structural and functional characterization of factor H mutations associated with atypical hemolytic uremic syndrome Am J Hum Genet 71 1285 1295 1:CAS:528:DC%2BD3sXjsV2n 10.1086/344515 12424708