Genetics of HUS: The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome

Jessica Caprioli, Marina Noris, Simona Brioschi, Gaia Pianetti, Federica Castelletti, Paola Bettinaglio, Caterina Mele, Elena Bresin, Linda Cassis, Sara Gamba, Francesca Porrati, Sara Bucchioni, Giuseppe Monteferrante, Celia J. Fang, M. K. Liszewski, David Kavanagh, John P. Atkinson, Giuseppe Remuzzi

Research output: Contribution to journalArticle

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Abstract

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy with manifestations of hemolytic anemia, thrombocytopenia, and renal impairment. Genetic studies have shown that mutations in complement regulatory proteins predispose to non-Shiga toxin-associated HUS (non-Stx-HUS). We undertook genetic analysis on membrane cofactor protein (MCP), complement factor H (CFH), and factor I (IF) in 156 patients with non-Stx-HUS. Fourteen, 11, and 5 new mutational events were found in MCP, CFH, and IF, respectively. Mutation frequencies were 12.8%, 30.1%, and 4.5% for MCP, CFH, and IF, respectively. MCP mutations resulted in either reduced protein expression or impaired C3b binding capability. MCP-mutated patients had a better prognosis than CFH-mutated and nonmutated patients. In MCP-mutated patients, plasma treatment did not impact the outcome significantly: remission was achieved in around 90% of both plasma-treated and plasma-untreated acute episodes. Kidney transplantation outcome was favorable in patients with MCP mutations, whereas the outcome was poor in patients with CFH and IF mutations due to disease recurrence. This study documents that the presentation, the response to therapy, and the outcome of the disease are influenced by the genotype. Hopefully this will translate into improved management and therapy of patients and will provide the way to design tailored treatments.

Original languageEnglish
Pages (from-to)1267-1279
Number of pages13
JournalBlood
Volume108
Issue number4
DOIs
Publication statusPublished - Aug 15 2006

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CD46 Antigens
Complement Factor H
Hemolytic-Uremic Syndrome
Mutation
Plasmas
Thrombotic Microangiopathies
Hemolytic Anemia
Mutation Rate
Therapeutics
Genetics
Thrombocytopenia
Kidney Transplantation
Complement System Proteins
Proteins
Genotype
Kidney
Recurrence

ASJC Scopus subject areas

  • Hematology

Cite this

Genetics of HUS : The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. / Caprioli, Jessica; Noris, Marina; Brioschi, Simona; Pianetti, Gaia; Castelletti, Federica; Bettinaglio, Paola; Mele, Caterina; Bresin, Elena; Cassis, Linda; Gamba, Sara; Porrati, Francesca; Bucchioni, Sara; Monteferrante, Giuseppe; Fang, Celia J.; Liszewski, M. K.; Kavanagh, David; Atkinson, John P.; Remuzzi, Giuseppe.

In: Blood, Vol. 108, No. 4, 15.08.2006, p. 1267-1279.

Research output: Contribution to journalArticle

Caprioli, J, Noris, M, Brioschi, S, Pianetti, G, Castelletti, F, Bettinaglio, P, Mele, C, Bresin, E, Cassis, L, Gamba, S, Porrati, F, Bucchioni, S, Monteferrante, G, Fang, CJ, Liszewski, MK, Kavanagh, D, Atkinson, JP & Remuzzi, G 2006, 'Genetics of HUS: The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome', Blood, vol. 108, no. 4, pp. 1267-1279. https://doi.org/10.1182/blood-2005-10-007252
Caprioli, Jessica ; Noris, Marina ; Brioschi, Simona ; Pianetti, Gaia ; Castelletti, Federica ; Bettinaglio, Paola ; Mele, Caterina ; Bresin, Elena ; Cassis, Linda ; Gamba, Sara ; Porrati, Francesca ; Bucchioni, Sara ; Monteferrante, Giuseppe ; Fang, Celia J. ; Liszewski, M. K. ; Kavanagh, David ; Atkinson, John P. ; Remuzzi, Giuseppe. / Genetics of HUS : The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. In: Blood. 2006 ; Vol. 108, No. 4. pp. 1267-1279.
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AU - Pianetti, Gaia

AU - Castelletti, Federica

AU - Bettinaglio, Paola

AU - Mele, Caterina

AU - Bresin, Elena

AU - Cassis, Linda

AU - Gamba, Sara

AU - Porrati, Francesca

AU - Bucchioni, Sara

AU - Monteferrante, Giuseppe

AU - Fang, Celia J.

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