Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation

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dc.contributor.authorMullighan, C.
dc.contributor.authorHeatley, S.
dc.contributor.authorDoherty, K.
dc.contributor.authorSzabo, F.
dc.contributor.authorGrigg, A.
dc.contributor.authorHughes, T.
dc.contributor.authorSchwarer, A.
dc.contributor.authorSzer, J.
dc.contributor.authorTait, B.
dc.contributor.authorTo, L.
dc.contributor.authorBardy, P.
dc.date.issued2002
dc.descriptionCopyright © 2002 by The American Society of Hematology.
dc.description.abstractLife-threatening complications such as graft versus host disease and infection remain major barriers to the success of allogeneic hemopoietic stem cell transplantation (SCT). While pretransplantation conditioning and posttransplantation immunosuppression are important risk factors for infection, the reasons that similarly immunosuppressed transplant recipients show marked variation in frequency of infection after allogeneic SCT are unclear. Mannose-binding lectin (MBL) deficiency is a risk factor for infection in other situations where immunity is compromised. We investigated associations between MBL2 gene polymorphisms and risk of major infection following allogeneic SCT. Ninety-seven related allogeneic donor-recipient pairs were studied. Clinical data including survival, days of fever, graft versus host disease incidence and severity, and infection were collected by case note review. Five single-nucleotide polymorphisms in the MBL2 gene were genotyped using the polymerase chain reaction and sequence-specific primers. MBL2 coding mutations were associated with an increased risk of major infection following transplantation. This association was seen for donor (P =.002, odds ratio [OR] 4.1) and recipient (P =.04, OR 2.6) MBL2 genotype. MBL2 promoter variants were also associated with major infection. The high-producing haplotype HYA was associated with a markedly reduced risk of infection (recipient HYA P =.0001, OR 0.16; donor HYA P =.001, OR 0.23). Donor MBL2 coding mutations and recipient HYA haplotype were independently associated with infection in multivariate analysis. These results suggest that MBL2 genotype influences the risk of infection following allogeneic SCT and that both donor and recipient MBL2 genotype are important. These findings raise the possibility that MBL replacement therapy may be useful following transplantation.
dc.description.statementofresponsibilityCharles G. Mullighan, Sue Heatley, Kathleen Doherty, Ferenc Szabo, Andrew Grigg, Timothy P. Hughes, Anthony P. Schwarer, Jeff Szer, Brian D. Tait, L. Bik To, and Peter G. Bardy
dc.identifier.citationBlood, 2002; 99(10):3524-3529
dc.identifier.doi10.1182/blood.V99.10.3524
dc.identifier.issn0006-4971
dc.identifier.issn1528-0020
dc.identifier.orcidMullighan, C. [0000-0002-1871-1850]
dc.identifier.orcidHeatley, S. [0000-0001-7497-6477]
dc.identifier.orcidHughes, T. [0000-0002-0910-3730] [0000-0002-7990-4509]
dc.identifier.urihttp://hdl.handle.net/2440/9304
dc.language.isoen
dc.publisherAmer Soc Hematology
dc.source.urihttp://bloodjournal.hematologylibrary.org/cgi/content/abstract/99/10/3524
dc.subjectHumans
dc.subjectGenetic Predisposition to Disease
dc.subjectCarrier Proteins
dc.subjectMannose-Binding Lectin
dc.subjectMannose-Binding Lectins
dc.subjectTreatment Outcome
dc.subjectHematopoietic Stem Cell Transplantation
dc.subjectTransplantation, Homologous
dc.subjectRetrospective Studies
dc.subjectGenotype
dc.subjectPolymorphism, Genetic
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectMulticenter Studies as Topic
dc.subjectInfections
dc.titleMannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation
dc.typeJournal article
pubs.publication-statusPublished

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