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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-04-1033. This Article Full Text (PDF) All Versions of this Article: 2002-04-1033v1 100/12/3908    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rocha, V Articles by Gluckman, E Search for Related Content PubMed PubMed Citation Articles by Rocha, V Articles by Gluckman, E Social Bookmarking                   What's this? Submitted April 22, 2002 Accepted July 3, 2002 HOST DEFENSE AND INFLAMMATORY GENE POLYMORPHISMS ARE ASSOCIATED WITH OUTCOMES AFTER HLA-IDENTICAL SIBLING BONE MARROW TRANSPLANT V Rocha*, R F Franco, R Porcher, H Bittencourt, W A Silva-Jr, A Latouche, A Devergie, H Esperou, P Ribaud, G Socie, M A Zago, and E Gluckman Hematology Department and Bone Marrow Transplant Unit, Hopital Saint Louis, Paris, France Center for Cell Therapy, Faculty of Medicine of Ribeirao Preto, Ribeirao Preto, Sao Paulo, Brazil Biostatistics, Hopital Saint Louis, Paris, France * Corresponding author; email: vanderson.rocha{at}sls.ap-hop-paris.fr. We made the hypothesis that donor (D) and recipient (R) gene polymorphisms that drive the host response to microorganisms could be associated with infections after bone marrow transplant (BMT). Patients and Methods: HLA-identical BMTs were performed for patients with acute (n=39) or chronic leukemias (n=68). Genotyping was performed in 107 D/R DNA pairs for gene polymorphisms of cytokines [(TNF- and ß), IL-1 receptor antagonist (IL-1Ra), IL-6 and IL-10)], adhesion molecules (CD31 and CD54), Fcreceptors (FcRIIa, IIIa, IIIb), mannose-binding lectin (MBL) and myeloperoxidase (MPO). First infection (overall) and first episodes of bacterial, viral, or invasive fungal infections were studied retrospectively during 180 days after BMT. Univariable and multivariable analyses, using death as competing event, were performed to study risk factors. Results: In a multivariable analysis, first overall infections were increased in patients with the FcRIIa R-131 genotype (Hazard Ratio (HR)=1.92; p=0.04) and severe bacterial infections were increased when the MPO donor genotype was AG or AA (HR=2.16; p=0.03). Viral and invasive fungal infections were not influenced by any genetic factor studied. Interestingly, we also found that: i) time to neutrophil recovery was shorter when donors were FcRIIIb HNA-1a/HNA-1b (HR=0.56; p=0.002), ii) donor IL-1Ra (absence of IL-1RN*2) increased the risk of acute GvHD (II-IV) (HR=2.17; p=0.017) and iii) recipient IL-10 (GG) and IL-1Ra genotype increased the risk of chronic GvHD (p=0.03 and 0.03, respectively). Finally, 180-day transplant-related mortality was increased when donors were FcRIIIb HNA-1a/HNA-1a or HNA-1b/HNA-1b (HR=2.57; p=0.05), and donor MPO genotype was AA (HR=5.14, p=0.004). In conclusion, D and R genes polymorphisms are informative genetic risk factors for selecting donor recipient pairs and could help in the understanding of mechanisms involved in host defenses of BMT recipients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. L. Espinoza, A. Takami, M. Onizuka, H. Sao, H. Akiyama, K. Miyamura, S. Okamoto, M. Inoue, Y. Kanda, S. 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