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Blood, 15 May 2002, Vol. 99, No. 10, pp. 3524-3529
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Mannose-binding lectin gene polymorphisms are associated with
major infection following allogeneic hemopoietic stem cell
transplantation
Charles 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
From Research and Development, Australian Red Cross
Blood Service, South Australia; and Haematology, Institute of
Medical and Veterinary Science; both of Adelaide, Australia; Bone
Marrow Transplant Programme, Alfred Hospital, Melbourne, Australia;
Bone Marrow Transplant Service, Department of Clinical Haematology and
Medical Oncology, Royal Melbourne Hospital; and Victorian
Transplantation and Immunogenetic Service, Australian Red Cross Blood
Service Victoria; both of Parkville, Australia.
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.

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