This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Fremeaux-Bacchi V, Dragon-Durey MA, Blouin J, Vigneau C, Kuypers D, Boudailliez B, Loirat C, Rondeau E, Fridman WH (2004) Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome. J Med Genet 41: e84
Kavanagh D, Kemp EJ, Mayland E, Winney RJ, Duffield JS, Warwick G, Richards A, Ward R, Goodship JA, Goodship TH (2005) Mutations in complement Factor I predispose to development of atypical hemolytic uremic syndrome. J Am Soc Nephrol 16: 2150–2155
Richards A, Kemp EJ, Liszewski MK, Goodship JA, Lampe AK, Decorte R, Muslumanoglu MH, Kavukcu S, Filler G, Pirson Y et al (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
Noris M, Brioschi S, Caprioli J, Todeschini M, Bresin E, Porrati F, Gamba S, Remuzzi G; International Registry of Recurrent and Familial HUS/TTP (2003) Familial haemolytic uraemic syndrome and an MCP mutation. Lancet 362: 1542–1547
Dragon-Durey MA, Loirat C, Cloarec S, Macher MA, Blouin J, Nivet H, Weiss L, Fridman WH, Fremeaux-Bacchi V (2005) Anti-Factor H autoantibodies associated with atypical hemolytic uremic syndrome. J Am Soc Nephrol 16: 555–563
Zipfel PF, Neumann HP, Józsi M (2003) Genetic screening in haemolytic uraemic syndrome. Curr Opin Nephrol Hypertens 12: 653–657
Gasser C, Gautier E, Steck A, Siebenmann RE, Dechslin R (1955) Hämolytisch-urämische syndrome bilaterale Nierenrindennekrosen bei akuten erworbenen hämolytischen Anämien. Schweiz Med Wschr 85: 905–909
Moake JL (2001) Thrombotic Microangiopathies. N Engl J Med 347: 589–600
Siegler R, Oakes R (2005) Hemolytic uremic syndrome; pathogenesis, treatment, and outcome. Curr Opin Pediatr 17: 200–204
Noris M, Remuzzi G (2005) Hemolytic uremic syndrome. J Am Soc Nephrol 16:1035–1050
Kaplan BS, Chesney RW, Drummond KN (1975) Hemolytic uremic syndrome in families. N Engl J Med 292: 1090–1093
Noris M, Ruggenenti P, Perna A, Orisio S, Caprioli J, Skerka C, Vasile B, Zipfel PF, Remuzzi G (1999) Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura. J Am Soc Nephrol 10: 281–293
Thompson RA, Winterborn MH (1981) Hypocomplementemia due to a genetic deficiency of b1H globulin. Clin Exp Immunol 46: 110–119
Pichette V, Querin, S, Schürich W, Brun G, Lehner-Netsch G, Delaghe J-M (1994) Familial hemolytic-uremic syndrome and homozygous factor H deficiency. Am J Kidney Dis 26: 936–941
Rougier N, Kazatchkine MD, Rougier JP, Fremeaux-Bacchi V, Blouin J, Deschenes G, Soto B, Baudouin V, Pautard B, Proesmans W et al (1998) Human complement factor H deficiency associated with hemolytic uremic syndrome. J Am Soc Nephrol 9: 2318–2326
Ohali M, Shalev H, Schlesinger M, Katz Y, Kachko L, Carmi R, Sofer S, Landau D (1998) Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H. Pediatr Nephrol 12: 619–624
Warwicker P, Goodship TH, Donne RL, Pirson Y, Nicholls A, Ward RM, Turnpenny P, Goodship JA (1998) Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int 53: 836–844
Warwicker P, Donne RL, Goodship JA, Goodship TH, Howie AJ, Kumararatne DS, Thompson RA, Taylor CM (1999) Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency. Nephrol Dial Transplant 14: 1229–1233
Caprioli J, Bettinaglio P, Zipfel PF, Amadei B, Daina E, Gamba S, Skerka C, Marziliano N, Remuzzi G, Noris M; Italian Registry of Familial and Recurrent HUS/TTP (2001) 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 12: 297–307
Dragon-Durey MA, Fremeaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G, Coppo P, Herman Fridman W, Weiss L (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
Licht C, Weyersberg A, Heinen S, Stapenhorst L, Devenge J, Beck B, Waldherr R, Kirschfink M, Zipfel PF, Hoppe B (2005) 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 45: 415–421
Rodríguez de Córdoba S, Díaz-Guillén MA, Heine-Suñer D 1999) An integrated map of the human regulator of complement activation (RCA) gene cluster on 1q32. Mol Immunol 36: 803–808
Díaz-Guillén MA, Rodríguez de Córdoba S, Heine-Suñer D (1999) A radiation hybrid map of complement factor H and factor H-related genes. Immunogenetics 49: 549–552
Krushkal J, Bat O, Gigli I (2000) Evolutionary relationships among proteins encoded by the regulator of complement activation gene cluster. Mol Biol Evol 17: 1718–1730
Józsi M, Richter H, Loschmann J, Skerka C, Buck F, Beisiegel U, Erdei A, Zipfel PF (2005) FHR-4A: a new factor H-related protein is encoded by the human FHR-4 gene. Eur J Hum Genet 13: 321–329
Schwaeble W, Zwirner J, Schulz TF, Linke RP, Dierich MP, Weiss EH (1987) Human complement factor H: expression of an additional truncated gene product of 43 kDa in human liver. Eur J Immunol 17: 1485–1489
Zipfel PF, Skerka C (1994) Complement factor H and related proteins: an expanding family of complement-regulatory proteins? Immunol Today 15: 121–126
Friese MA, Hellwage J, Jokiranta TS, Meri S, Peter HH, Eibel H, Zipfel PF (1999) FHL-1/reconectin and factor H: two human complement regulators which are encoded by the same gene are differently expressed and regulated. Mol Immunol 36: 809–818
Rodríguez de Córdoba S, Rubinstein P (1984) Genetic polymorphism of human factor H (β1H). J Immunol 132: 1906–1908
Ripoche J, Day AJ, Harris TJ, Sim RB (1988) The complete amino acid sequence of human complement factor H. Biochem J 249: 593–602
Warwicker P, Goodship THJ, Goodship JA (1997) Three new polymorphisms in the human complement factor H gene and promoter region. Immunogenetics 46: 437–438
Neumann HP, Salzmann M, Bohnert-Iwan B, Mannuelian T, Skerka C, Lenk D, Bender BU, Cybulla M, Riegler P, Konigsrainer A et al (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
Caprioli J, Castelletti F, Bucchioni S, Bettinaglio P, Bresin E, Pianetti G, Gamba S, Brioschi S, Daina E, Remuzzi G, Noris M (2003) International Registry of Recurrent and Familial HUS/TTP. Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. Hum Mol Genet 12: 3385–3395
Fremeaux-Bacchi V, Kemp EJ, Goodship JA, Dragon-Durey MA, Strain L, Loirat C, Deng HW, Goodship TH (2005) The development of atypical HUS is influenced by susceptibility factors in factor H and membrane cofactor protein-evidence from two independent cohorts. J Med Genet 2005 Mar 22; [Epub ahead of print]
Esparza-Gordillo J, Goicoechea de Jorge E, Buil A, Carreras Berges L, Lopez-Trascasa M, Sanchez-Corral P, Rodriguez de Cordoba S (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
Kristensen T, Tack BF (1986) Murine protein H is comprised of 20 repeating units, 61 amino acids in length. Proc Natl Acad Sci USA 83: 3963–3967
Norman DG, Barlow PN, Baron M, Day AJ, Sim RB, Campbell D (1991) Three dimensional structure of a complement control protein module in solution. J Mol Biol 219: 717–725
Nilsson UR, Müller-Eberhard HJ (1965) Isolation of β1F-globulin from human serum and its characterization as the fifth component of complement. J Exp Med 122: 277–298
Whaley K, Ruddy S (1976) Modulation of the alternative complement pathway by beta 1H globulin. J Exp Med 144: 1147–1163
Weiler JM, Daha MR, Austen KF, Fearon DT (1976) Control of the amplification convertase of complement by the plasma protein beta1H. Proc Natl Acad Sci USA 73: 3268–3272
Pangburn MK, Schreiber RD, Müller-Eberhard HJ (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
Pangburn MK (2002) Cutting edge: localization of the host recognition functions of complement factor H at the carboxyl-terminal: implications for hemolytic uremic syndrome. J Immunol 169: 4702–4706
Manuelian T, Hellwage J, Meri S, Caprioli J, Noris M, Heinen S, Józsi M, Neumann HP, Remuzzi G, Zipfel PF (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
Józsi M, Manuelian T, Heinen S, Oppermann M, Zipfel PF (2004) Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relevance for pathology. Histol Histopathol 19: 251–258
Conrad DH, Carlo JR, Ruddy S (1978) Interaction of beta1H globulin with cell-bound C3b: quantitative analysis of binding and influence of alternative pathway components on binding. J Exp Med 147: 1792–1805
Jokiranta TS, Zipfel PF, Hakulinen J, Kuhn S, Pangburn MK, Tamerius JD, Meri S (1996) Analysis of the recognition mechanism of the alternative pathway of complement by monoclonal anti-factor H antibodies: evidence for multiple interactions between H and surface bound C3b. FEBS Lett 393: 297–302
Pangburn MK, Pangburn KL, Koistinen V, Meri S, Sharma AK (2000) Molecular mechanisms of target recognition in an innate immune system: interactions among factor H, C3b, and target in the alternative pathway of human complement. J Immunol 164: 4742–4751
Fearon DT (1978) Regulation by membrane sialic acid of beta1H-dependent decay-dissociation of amplification C3 convertase of the alternative complement pathway. Proc Natl Acad Sci USA 75: 1971–1975
Kazatchkine MD, Fearon DT, Austen KF (1979) Human alternative complement pathway: membrane-associated sialic acid regulates the competition between B and beta1 H for cell-bound C3b. J Immunol 122: 75–81
Meri S, Pangburn MK (1990) Discrimination between activators and nonactivators of the alternative pathway of complement: Regulation via a sialic acid/polyanion binding site on factor H. Proc Natl Acad Sci USA 87: 3982–3986
Pangburn MK, Atkinson MA, Meri S (1991) Localization of the heparin-binding site on complement factor H. J Biol Chem 266: 16847–16853
Meri S, Pangburn MK (1994) Regulation of alternative pathway complement activation by glycosaminoglycans: specificity of the polyanion binding site on factor H. Biochem Biophys Res Commun 198: 52–59
Blackmore TK, Sadlon, TA, Ward, HM, Lublin DM, Gordon, DL (1996) Identification of a heparin binding domain in the seventh short consensus repeat of complement factor H. J Immunol 157: 5422–5427
Blackmore TK, Hellwage J, Sadlon TA, Higgs N, Zipfel PF, Ward HM, Gordon DL (1998) Identification of the second heparin-binding domain in human complement factor H. J Immunol 160: 3342–3348
Ram S, Sharma AK, Simpson SD, Gulati S, McQuillen DP, Pangburn MK, Rice PA (1998) A novel sialic acid binding site on factor H mediates serum resistance of sialylated Neisseria gonorrhoeae. J Exp Med 187: 743–752
Pio R, Martinez A, Unsworth EJ, Kowalak JA, Bengoechea JA, Zipfel PF, Elsasser TH, Cuttitta F (2001) Complement factor H is a serum-binding protein for adrenomedullin, and the resulting complex modulates the bioactivities of both partners. J Biol Chem 276: 12292–12300
Jarva H, Jokiranta TS, Hellwage J, Zipfel PF, Meri S (1999) Regulation of complement activation by C-reactive protein: targeting the complement inhibitory activity of factor H by an interaction with short consensus repeat domains 7 and 8–11. J Immunol 163: 3957–3962
Zipfel PF, Hellwage J, Friese MA, Hegasy G, Jokiranta ST, Meri S (1999) Factor H and disease: a complement regulator affects vital body functions. Mol Immunol 36: 241–248
Lindahl G, Sjobring U, Johnsson E (2001) Human complement regulators: a major target for pathogenic microorganisms. Curr Opin Immunol 12: 576–582
Perkins SJ, Goodship TH (2002) Molecular modelling of the C-terminal domains of factor H of human complement: a correlation between haemolytic uraemic syndrome and a predicted heparin binding site. J Mol Biol 316: 217–224
Hellwage J, Jokiranta TS, Friese MA, Wolk TU, Kampen E, Zipfel PF, Meri S (2002). Complement C3b/C3d and cell surface polyanions are recognized by overlapping binding sites on the most carboxyl-terminal domain of complement factor H. J Immunol 169: 6935–6944
Ganesh VK, Smith SA, Kotwal GJ, Murthy KH. (2004) Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation. Proc Natl Acad Sci USA 101: 8924–8929
Jozsi M, Heinen S, Hartmann A, Ostrowicz CD, Hälbich S, Richter H, Kunert A, Licht C, Saunders RE, Perkins SJ et al (2005) Factor H and atypical hemolytic uremic syndrome: mutations in the C-terminus cause structural changes and defective recognition functions. JASN; in press
Sharma AK, Pangburn MK (1996) Identification of three physically and functionally distinct binding sites for C3b in human complement factor H by deletion mutagenesis. Proc Natl Acad Sci USA 93: 10996–11001
Jokiranta TS, Hellwage J, Koistinen V, Zipfel PF, Meri S (2000) Each of the three binding sites on complement factor H interacts with a distinct site on C3b. J Biol Chem 275: 27657–27662
Oppermann M, Manuelian T, Józsi M, Brandt E, Hellwage J, Jokiranta TS, Meri S, Skerka C, Götze O, Zipfel PF (2005) The C-terminus of complement regulator Factor H is central for target recognition: Evidence for a compact conformation of the native protein. Submitted
Ault BH, Schmidt BZ, Fowler NL, Kashtan CE, Ahmed AE, Vogt BA, Colten HR (1997) Human factor H deficiency. J Biol Chem 272: 25168–25175
Ying L, Katz Y, Schlesinger M, Carmi R, Shalev H, Haider N, Beck G, Sheffield VC, Landau D (1999) Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. Am J Hum Genet 65: 1538–1546
Buddles MR, Donne RL, Richards A, Goodship J, Goodship TH (2000) Complement factor H gene mutation associated with autosomal recessive atypical hemolytic uremic syndrome. Am J Hum Genet 66: 1721–1722
Perez-Caballero D, Gonzalez-Rubio C, Gallardo ME, Vera M, Lopez-Trascasa M, Rodriguez de Cordoba S, Sanchez-Corral P (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
Richards A, Buddles MR, Donne RL, Kaplan BS, Kirk E, Venning MC, Tielemans CL, Goodship JA, Goodship TH (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
Filler G, Radhakrishnan S, Strain L, Hill A, Knoll G, Goodship TH (2004) Challenges in the management of infantile factor H associated hemolytic uremic syndrome. Pediatr
de Paula PF, Barbosa JE, Junior PR, Ferriani VP, Latorre MR, Nudelman V, Isaac L (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
Sanchez-Corral P, Perez-Caballero D, Huarte O, Simckes AM, Goicoechea E, Lopez-Trascasa M, Rodriguez de Cordoba S (2002) Structural and functional characterization of factor H mutations associated with atypical hemolytic uremic syndrome. Ann J Hum Genet 71: 1285–1295
Kühn S, Skerka C, Zipfel PF (1995) Mapping of the complement regulatory domains in the human factor H-like protein 1 and in factor H1. J Immunol 155: 5663–5670
Lehtinen MJ, Meri S, Jokiranta TS (2004) Interdomain contact regions and angles between adjacent short consensus repeat domains. J Mol Biol 344: 1385–1396
Heinen S, Józsi M, Noris M, Remuzzi G, Zipfel PF (2006) An HUS associated mutant Factor H protein that lacks domain 20 shows reduced cofactor activity on the surface of endothelial cells. Mol Immunol 43: 165–166 [abstract]
Sanchez-Corral P, Gonzalez-Rubio C, Rodriguez de Cordoba S, Lopez-Trascasa M (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
Jokiranta TS, Westin J, Nilsson UR, Nilsson B, Hellwage J, Lofas S, Gordon DL, Ekdahl KN, Meri S (2001) Complement C3b interactions studied with surface plasmon resonance technique. Int Immunopharmacol 1: 495–506
Goodship TH, Liszewski MK, Kemp EJ, Richards A, Atkinson JP (2004) Mutations in CD46, a complement regulatory protein, predispose to atypical HUS. Trends Mol Med 10: 226–231
Liszewski MK, Farries TC, Lublin DM, Rooney IA, Atkinson JP (1996) Control of the complement system. Adv Immunol 61: 201–283
Cheong HI, Lee BS, Kang HG, Hahn H, Suh KS, Ha IS, Choi Y (2004) Attempted treatment of factor H deficiency by liver transplantation. Pediatr Nephrol 19: 454–458
Remuzzi G, Ruggenenti P, Codazzi D, Noris M, Caprioli J, Locatelli G, Gridelli B (2002) Combined kidney and liver transplantation for familial haemolytic uraemic syndrome. Lancet 359: 1671–1672
Rodriguez de Cordoba S, Esparza-Gordillo J, Goicoechea de Jorge E, Lopez-Trascasa M, Sanchez-Corral P (2004) The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol 41: 355–367
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Birkhäuser Verlag Basel/Switzerland
About this chapter
Cite this chapter
Skerka, C., Józsi, M. (2006). Role of complement and Factor H in hemolytic uremic syndrome. In: Zipfel, P.F. (eds) Complement and Kidney Disease. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7428-4_6
Download citation
DOI: https://doi.org/10.1007/3-7643-7428-4_6
Publisher Name: Birkhäuser Basel
Print ISBN: 978-3-7643-7166-1
Online ISBN: 978-3-7643-7428-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)