Mannose-binding lectin status is associated with risk of major infection following myeloablative sibling allogeneic hematopoietic stem cell transplantation.
Mannose-binding lectin (MBL) is a mediator of innate immunity that influences the risk of infection in a range of clinical settings. We previously reported associations between MBL2 genotype and infection in a retrospective study of myeloablative allogeneic hematopoietic stem cell transplantation (allo-HCT). However, other studies have been inconclusive, and the role of MBL in reduced-intensity conditioning (RIC) transplantation is unknown. Here we report a prospective study examining MBL2 genotype, MBL levels, and risk of major infection following HLA-matched sibling myeloablative (n = 83) and RIC (n = 59) HCT. Baseline MBL levels were higher in recipients than donors (P < .001), and recipient MBL levels increased during the peritransplantation period (P = .001), most notably in MBL2 wild-type individuals receiving myeloablative total body irradiation (mTBI). MBL2 coding mutations were associated with major infection in recipients receiving mTBI. The cumulative incidence of major infection in recipient harboring an MBL2 mutation receiving mTBI was 70.6%, compared with 31.1% of those without mutations not receiving mTBI (P = .01). MBL status was not associated with infection in RIC transplants. These results confirm the association of MBL status with risk of infection in myeloablative, TBI-conditioned transplantation. Studies examining the role of MBL replacement therapy to prevent infection in this setting should be considered.
Mullighan
Charles G
CG
Institute of Medical and Veterinary Science, Adelaide, Australia. charles.mullighan@stjude.org
Heatley
Susan L
SL
Danner
Silke
S
Dean
Melinda M
MM
Doherty
Kathleen
K
Hahn
Uwe
U
Bradstock
Kenneth F
KF
Minchinton
Robyn
R
Schwarer
Anthony P
AP
Szer
Jeff
J
Bardy
Peter G
PG
D000328:Adult; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000097:blood / Q000209:etiology / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007239:Infections / Q000097:blood / Q000209:etiology* / Q000235:genetics; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D035781:Siblings; D014184:Transplantation, Homologous
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin