title: Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation.
abstract: Life-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.
authors: Research and Development, Australian Red Cross Blood Service, South Australia. cmull@senet.com.au
authors: Charles G
authors: CG
authors: Mullighan
authors: Sue
authors: S
authors: Heatley
authors: Kathleen
authors: K
authors: Doherty
authors: Ferenc
authors: F
authors: Szabo
authors: Andrew
authors: A
authors: Grigg
authors: Timothy P
authors: TP
authors: Hughes
authors: Anthony P
authors: AP
authors: Schwarer
authors: Jeff
authors: J
authors: Szer
authors: Brian D
authors: BD
authors: Tait
authors: L
authors: L
authors: Bik To
authors: Peter G
authors: PG
authors: Bardy
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007239:Infections / Q000209:etiology / Q000235:genetics*; D008297:Male; D037601:Mannose-Binding Lectin / Q000031:analogs & derivatives*; D037241:Mannose-Binding Lectins; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D037241:Mannose-Binding Lectins