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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4865-4870. Prepublished online as a Blood First Edition Paper on March 9, 2006; DOI 10.1182/blood-2005-07-2820. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-2820v1 107/12/4865    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 Citing Articles via Google Scholar Google Scholar Articles by Sprong, T. Articles by van Deuren, M. Search for Related Content PubMed PubMed Citation Articles by Sprong, T. Articles by van Deuren, M. Related Collections Clinical Trials and Observations Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections Tom Sprong, Dirk Roos, Corry Weemaes, Chris Neeleman, Christel L. M. Geesing, Tom Eirik Mollnes, and Marcel van Deuren From the Department of General Internal Medicine, Pediatrics, and Intensive Care, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; Nijmegen University Centre for Infectious Diseases, Nijmegen, the Netherlands; Sanquin Research at the Central Laboratory of the Netherlands Blood Transfusion Service (CLB), and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, the Netherlands; Department of Pediatrics, Bernhoven hospital, Oss, the Netherlands; and the Institute of Immunology, Rikshospitalet University Hospital, University of Oslo, Norway. The complement system is an essential element in our innate defense against infections with Neisseria meningitidis. We describe 2 cases of meningococcal septic shock, 1 of them fatal, in 2 children of a Turkish family. In the surviving patient, alternative pathway activation was absent and factor D plasma concentrations were undetectable. Concentrations of mannose-binding lectin (MBL), C1q, C4 and C3, factor B, properdin, factor H, and factor I were normal. Mutation analysis of the factor D gene revealed a T638 > G (Val213 > Gly) and a T640 > C (Cys214 > Arg) mutation in the genomic DNA from the patient, both in homozygous form. The consanguineous parents and an unaffected sister had these mutations in heterozygous form. In vitro incubation of factor-D–deficient plasma of the boy with serogroup B N meningitidis showed normal MBL-mediated complement activation but no formation of the alternative pathway C3-convertase C3bBbP, and severely decreased C3bc formation and terminal complement activation. The defect was restored after supplementation with factor D. In conclusion, this is the second report of a factor D gene mutation leading to factor D deficiency in a family with meningococcal disease. This deficiency abolishes alternative-pathway dependent complement activation by N meningitidis, and leads to an increased susceptibility to invasive meningococcal disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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