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.

CONCLUSION:

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: Miquel Granell, Alvaro Urbano-Ispizua, Belén Suarez, Montserrat Rovira, Francesc Fernández-Avilés, Carmen Martínez, Mar Ortega, Carla Uriburu, Anna Gaya, Josep M A Roncero, Alfons Navarro, Enric Carreras, Josep Mensa, Jordi Vives, Ciril Rozman, Emili Montserrat, Francisco Lozano
• Journal: Experimental hematology (Exp Hematol) Vol. 34 Issue 10 Pg. 1435-41 (Oct 2006) ISSN: 0301-472X [Print] Netherlands
• PMID: 16982337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Complement C2
• Complement C4
• MBL2 protein, human
• Mannose-Binding Lectin
• MASP2 protein, human
• Mannose-Binding Protein-Associated Serine Proteases

Topics

• Acute Disease
• Adult
• Complement C2 (genetics, metabolism)
• Complement C4 (genetics, metabolism)
• Complement Pathway, Mannose-Binding Lectin (genetics)
• DNA Mutational Analysis (methods)
• Exons (genetics)
• Female
• Genetic Predisposition to Disease
• Genotype
• Graft vs Host Disease (etiology, genetics, metabolism)
• Hematologic Neoplasms (complications, genetics, therapy)
• Humans
• Male
• Mannose-Binding Lectin (genetics, metabolism)
• Mannose-Binding Protein-Associated Serine Proteases (genetics, metabolism)
• Middle Aged
• Mycoses (etiology, genetics, metabolism)
• Polymorphism, Genetic
• Predictive Value of Tests
• Prognosis
• Promoter Regions, Genetic (genetics)
• Stem Cell Transplantation (adverse effects)
• Tissue Donors
• Transplantation, Homologous