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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3167-3172. Prepublished online as a Blood First Edition Paper on December 27, 2005; DOI 10.1182/blood-2005-09-3918. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-09-3918v1 107/8/3167    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Astermark, J. Articles by Lefvert, A.-K. Search for Related Content PubMed PubMed Citation Articles by Astermark, J. Articles by Lefvert, A.-K. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Free Research Articles Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Polymorphisms in the IL10 but not in the IL1beta and IL4 genes are associated with inhibitor development in patients with hemophilia A Jan Astermark, Johannes Oldenburg, Anna Pavlova, Erik Berntorp, Ann-Kari Lefvert, for the MIBS Study Group From the Department for Coagulation Disorders, Malmö University Hospital, Malmö, Sweden; Institute of Transfusion Medicine and Immunohaematology, University Clinic, Frankfurt; Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Germany; and Immunological Research Laboratory, Center for Molecular Medicine and Department of Medicine, Karolinska Institute, Stockholm, Sweden. The aim of the Malmö International Brother Study (MIBS) is to evaluate host genetic factors associated with the development of inhibitory antibodies in patients with hemophilia. Factor VIII gene mutations and genetic polymorphisms of the IL1beta, IL4, and IL10 genes, known to influence antibody production in autoimmune diseases, were analyzed in 164 patients (124 with severe, 26 with moderate, and 14 with mild disease) in 78 unrelated families with hemophilia A. Seventy-seven (47%) patients in 54 families had a history of inhibitors (57 high responding, 20 low responding). Inversions were found in 36 families (75 patients). There was no association between the development of inhibitor and the IL1beta Taq I RFLP alleles in exon 5 or the –590 C/T single nucleotide polymorphism (SNP) in the promoter region of IL4. There was, however, a strong association between an allele with 134 bp in one of the CA repeat microsatellites, IL10G, located in the promoter region of the IL10 gene, and the development of inhibitor (odds ratio [OR], 4.4; 95% confidence interval [95% CI], 2.1-9.5; P < .001). The association was consistent in the subgroup of families with severe hemophilia and inversions. IL10 is the first gene located outside the causative factor VIII gene mutation to be associated with inhibitor development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: "Selfless" cytokines, fraternal discord, and inhibitors W. Keith Hoots Blood 2006 107: 3024-3025. [Full Text] [PDF] This article has been cited by other articles: S. Lacroix-Desmazes, A.-M. Navarrete, S. Andre, J. Bayry, S. V. Kaveri, and S. Dasgupta Dynamics of factor VIII interactions determine its immunologic fate in hemophilia A Blood, July 15, 2008; 112(2): 240 - 249. [Abstract] [Full Text] [PDF] S. C. Gouw, J. G. van der Bom, G. Auerswald, C. E. Ettinghausen, U. Tedgard, H. M. van den Berg, and for the CANAL Study group Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study Blood, June 1, 2007; 109(11): 4693 - 4697. [Abstract] [Full Text] [PDF] S. C. Gouw, J. G. van der Bom, H. Marijke van den Berg, and for the CANAL Study group Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study Blood, June 1, 2007; 109(11): 4648 - 4654. [Abstract] [Full Text] [PDF] J. Astermark, J. Oldenburg, J. Carlson, A. Pavlova, K. Kavakli, E. Berntorp, A.-K. Lefvert, and for the MIBS Study Group Polymorphisms in the TNFA gene and the risk of inhibitor development in patients with hemophilia A Blood, December 1, 2006; 108(12): 3739 - 3745. [Abstract] [Full Text] [PDF] D. Lillicrap The Role of Immunomodulation in the Management of Factor VIII Inhibitors Hematology, January 1, 2006; 2006(1): 421 - 425. [Abstract] [Full Text] [PDF]

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