title: Mannan-binding lectin pathway deficiencies and invasive fungal infections following allogeneic stem cell transplantation.
abstract: OBJECTIVE
  The Mannan-binding lectin (MBL) pathway involves recognition of fungal surfaces by MBL and cleavage of C2 and C4 by MBL-associated serine protease (namely, MASP-2). Recent data show that MBL pathway deficiency might result not only from polymorphisms of the MBL2 gene but also of MASP2. The aim of the study was to assess whether polymorphisms of these genes are associated with invasive fungal infections (IFIs) following allogeneic stem cell transplantation (allo-SCT).
  
  
  METHODS
  The promoter and the exon 1 of MBL2 and the exon 3 of MASP2 were sequenced in 106 donor-recipient pairs from HLA-identical sibling allo-SCTs performed in a single institution.
  
  
  RESULTS
  Ten percent of the donors and 11% of the recipients carried the MBL-low (O/O, LXA/O) genotypes; 7% of the donors and 3% of the recipients were heterozygous for the MASP2 Asp105Gly variant. Factors associated with a higher probability of IFIs were donor's MBL-low genotype (38% vs 12%, p = 0.01), recipient's MASP2 variant (67% vs 14%, p = 0.01), and acute graft-versus-host disease (GVHD) grades II to IV (27% vs 11%, p = 0.04); in the multivariate analysis MBL-low genotype (relative risk [RR] 7.3, p = 0.003), MASP2 variant (RR 6.4, p = 0.002), and acute GVHD II to IV (RR 3.8, p = 0.02) retained independent prognostic value.
  
  
  CONCLUSIONS
  These results show for the first time that polymorphisms responsible for not only MBL but also MASP-2 deficiency are independent predictive factors for IFI after allo-SCT.
authors.affiliation: Departments of Hematology, Hospital Clínic of Barcelona, Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Granell
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: Belén
authors.initials: B
authors.lastname: Suarez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.forename: Francesc
authors.initials: F
authors.lastname: Fernández-Avilés
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Mar
authors.initials: M
authors.lastname: Ortega
authors.forename: Carla
authors.initials: C
authors.lastname: Uriburu
authors.forename: Anna
authors.initials: A
authors.lastname: Gaya
authors.forename: Josep M A
authors.initials: JM
authors.lastname: Roncero
authors.forename: Alfons
authors.initials: A
authors.lastname: Navarro
authors.forename: Enric
authors.initials: E
authors.lastname: Carreras
authors.forename: Josep
authors.initials: J
authors.lastname: Mensa
authors.forename: Jordi
authors.initials: J
authors.lastname: Vives
authors.forename: Ciril
authors.initials: C
authors.lastname: Rozman
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: Francisco
authors.initials: F
authors.lastname: Lozano
mesh_terms: D000208:Acute Disease; D000328:Adult; D003175:Complement C2 / Q000235:genetics / Q000378:metabolism; D003181:Complement C4 / Q000235:genetics / Q000378:metabolism; D037582:Complement Pathway, Mannose-Binding Lectin / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000150:complications / Q000235:genetics / Q000628:therapy; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009181:Mycoses / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D033581:Stem Cell Transplantation / Q000009:adverse effects; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D003175:Complement C2; D003181:Complement C4; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases