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

Miquel Granell1, Alvaro Urbano-Ispizua, Belén Suarez

  • 1Departments of Hematology, Hospital Clínic of Barcelona, Barcelona, Spain.

Experimental Hematology
|September 20, 2006
PubMed
Abstract

Insights

Genetic variations in Mannan-binding lectin (MBL) and MASP-2 impact invasive fungal infections (IFIs) after stem cell transplants. MBL pathway deficiencies in donors or recipients increase IFI risk post-transplant.

Area of Science:

  • Immunology
  • Genetics
  • Transplantation Medicine

Background:

  • The Mannan-binding lectin (MBL) pathway is crucial for innate immunity, recognizing fungal surfaces via MBL and activating complement through MBL-associated serine proteases (MASPs).
  • Deficiencies in the MBL pathway can arise from genetic polymorphisms in MBL2 and MASP2 genes, potentially affecting immune response.
  • Invasive fungal infections (IFIs) pose a significant risk to patients undergoing allogeneic stem cell transplantation (allo-SCT).

Purpose of the Study:

  • To investigate the association between polymorphisms in the MBL2 and MASP2 genes and the incidence of IFIs in patients following allo-SCT.
  • To identify genetic factors that may predict the risk of developing IFIs after allo-SCT.

Main Methods:

  • Sequencing of the MBL2 promoter and exon 1, and MASP2 exon 3 in 106 donor-recipient pairs undergoing HLA-identical sibling allo-SCT.
  • Genotyping for MBL-low (O/O, LXA/O) and MASP2 Asp105Gly variant.

Main Results:

  • MBL-low genotypes were found in 10% of donors and 11% of recipients; the MASP2 Asp105Gly variant was present in 7% of donors and 3% of recipients.
  • Donor MBL-low genotype (38% vs 12%), recipient MASP2 variant (67% vs 14%), and acute GVHD grades II-IV (27% vs 11%) were associated with higher IFI probability.
  • Multivariate analysis confirmed MBL-low genotype (RR 7.3), MASP2 variant (RR 6.4), and acute GVHD II-IV (RR 3.8) as independent predictors of IFI.

Conclusions:

  • Genetic polymorphisms affecting MBL and MASP-2 function are independent predictive factors for IFIs after allo-SCT.
  • These findings highlight the role of the MBL pathway in antifungal immunity post-transplantation and offer potential targets for risk stratification.

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