Mannose binding lectin and ficolin-2 polymorphisms are associated with increased risk for bacterial infections in children with B acute lymphoblastic leukemia

Pediatr Blood Cancer. 2014 Jun;61(6):1017-22. doi: 10.1002/pbc.24951. Epub 2014 Jan 22.

Abstract

Background: We aimed to investigate whether the presence of mannose binding lectin (MBL2), ficolin 2 (FCN2) polymorphisms or the combined deficiency significantly influence the risk and subsequently the frequency of chemotherapy-induced bacterial infections in children with B acute lymphoblastic leukemia (B-ALL).

Procedure: MBL2 polymorphisms for exon 1 and FCN2 polymorphisms for promoter regions -986, -602, -557, -64, -4 and exon 8 regions +6,359, +6,424 were determined in children with B-ALL. FCN2 haplotype was determined by gene sequencing. Number and duration of FN episodes as well as number of bacterial infections were recorded during induction chemotherapy.

Results: Forty-four children with B-ALL (median age 4.3 years, 65.9% males) suffered from 142 FN episodes and 92 bacterial infections (40.2% Gram positive and 59.8% Gram negative). MBL2 low-risk genotype was found in 59.1%, medium-risk in 31.8% and high-risk in 9%. FCN2 low-risk haplotypes were detected in 38.2%, medium-risk in 44.1% and high-risk in 17.6%. MBL2 genotype and FCN2 haplotype were not associated with increased frequency of FN episodes. MBL2 medium/high-risk genotype and FCN2 medium/high-risk haplotype were associated with prolonged duration of FN (P = 0.007 and P = 0.001, respectively) and increased number of bacterial infections (P = 0.001 and P = 0.002, respectively). The combined MBL2/FCN2 medium/high-risk genotype was associated with an increased number of bacterial infections (P = 0.001).

Conclusions: MBL2 and FCN2 single or combined deficiencies are associated with increased duration of FN episodes as well as increased number of bacterial infections in children with B-ALL suggesting a prognostic role of these genes.

Keywords: B-ALL ;bacterial infections; MBL polymorphisms; ficolin L gene polymorphisms; immunosuppression; pattern recognition receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bacterial Infections / etiology
  • Bacterial Infections / genetics*
  • Child
  • Child, Preschool
  • Codon / genetics
  • Exons / genetics
  • Febrile Neutropenia / chemically induced
  • Febrile Neutropenia / genetics*
  • Female
  • Ficolins
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Immunity, Innate
  • Immunocompromised Host
  • Infant
  • Lectins / deficiency
  • Lectins / genetics
  • Lectins / physiology*
  • Male
  • Mannose-Binding Lectin / deficiency
  • Mannose-Binding Lectin / genetics
  • Mannose-Binding Lectin / immunology
  • Mannose-Binding Lectin / physiology*
  • Metabolism, Inborn Errors / complications
  • Metabolism, Inborn Errors / immunology
  • Polymorphism, Genetic*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Risk

Substances

  • Codon
  • Lectins
  • MBL2 protein, human
  • Mannose-Binding Lectin

Supplementary concepts

  • Mannose-Binding Protein Deficiency