SEARCH:   Advanced

Blood, 5 November 2009, Vol. 114, No. 19, pp. 4261-4271. Prepublished online as a Blood First Edition Paper on September 10, 2009; DOI 10.1182/blood-2009-05-223834. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2009-05-223834v1 114/19/4261    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Abarrategui-Garrido, C. Articles by Sánchez-Corral, P. PubMed PubMed Citation Articles by Abarrategui-Garrido, C. Articles by Sánchez-Corral, P. Related Collections Immunobiology Thrombosis and Hemostasis Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Characterization of complement factor H–related (CFHR) proteins in plasma reveals novel genetic variations of CFHR1 associated with atypical hemolytic uremic syndrome Cynthia Abarrategui-Garrido1,*, Rubén Martínez-Barricarte2,*, Margarita López-Trascasa3, Santiago Rodríguez de Córdoba2, and Pilar Sánchez-Corral1 1 Research Unit, Hospital Universitario La Paz and Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid; 2 Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Centro de Investigación Biomédica en Red de Enfermedades Raras and Instituto Reina Sofía de Investigaciones Nefrológicas, Madrid; and 3 Immunology Unit, Hospital Universitario La Paz and Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain The factor H–related protein family (CFHR) is a group of minor plasma proteins genetically and structurally related to complement factor H (fH). Notably, deficiency of CFHR1/CFHR3 associates with protection against age-related macular degeneration and with the presence of anti-fH autoantibodies in atypical hemolytic uremic syndrome (aHUS). We have developed a proteomics strategy to analyze the CFHR proteins in plasma samples from controls, patients with aHUS, and patients with type II membranoproliferative glomerulonephritis. Here, we report on the identification of persons carrying novel deficiencies of CFHR1, CFHR3, and CFHR1/CFHR4A, resulting from point mutations in CFHR1 and CFHR3 or from a rearrangement involving CFHR1 and CFHR4. Remarkably, patients with aHUS lacking CFHR1, but not those lacking CFHR3, present anti-fH autoantibodies, suggesting that generation of these antibodies is specifically related to CFHR1 deficiency. We also report the characterization of a novel CFHR1 polymorphism, resulting from a gene conversion event between CFH and CFHR1, which strongly associates with aHUS. The risk allotype CFHR1*B, with greater sequence similarity to fH, may compete with fH, decreasing protection of cellular surfaces against complement damage. In summary, our comprehensive analyses of the CFHR proteins have improved our understanding of these proteins and provided further insights into aHUS pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020