Mannan-binding lectin pathway deficiencies and invasive fungal infections following allogeneic stem cell transplantation

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 th...

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Published in:	Experimental hematology Vol. 34; no. 10; pp. 1435 - 1441
Main Authors:	Granell, Miquel, Urbano-Ispizua, Alvaro, Suarez, Belén, Rovira, Montserrat, Fernández-Avilés, Francesc, Martínez, Carmen, Ortega, Mar, Uriburu, Carla, Gaya, Anna, Roncero, Josep M a., Navarro, Alfons, Carreras, Enric, Mensa, Josep, Vives, Jordi, Rozman, Ciril, Montserrat, Emili, Lozano, Francisco
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Inc 01-10-2006
Subjects:	Acute Disease Adult Complement C2 - genetics Complement C2 - metabolism Complement C4 - genetics Complement C4 - metabolism Complement Pathway, Mannose-Binding Lectin - genetics DNA Mutational Analysis - methods Exons - genetics Female Genetic Predisposition to Disease Genotype Graft vs Host Disease - etiology Graft vs Host Disease - genetics Graft vs Host Disease - metabolism Hematologic Neoplasms - complications Hematologic Neoplasms - genetics Hematologic Neoplasms - therapy Humans Male Mannose-Binding Lectin - genetics Mannose-Binding Lectin - metabolism Mannose-Binding Protein-Associated Serine Proteases - genetics Mannose-Binding Protein-Associated Serine Proteases - metabolism Middle Aged Mycoses - etiology Mycoses - genetics Mycoses - metabolism Polymorphism, Genetic Predictive Value of Tests Prognosis Promoter Regions, Genetic - genetics Stem Cell Transplantation - adverse effects Tissue Donors Transplantation, Homologous
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Summary:	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). 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0301-472X 1873-2399
DOI:	10.1016/j.exphem.2006.06.005