4.4 Article

Mannose Binding Lectin and Ficolin-2 Polymorphisms are Associated With Increased Risk for Bacterial Infections in Children With B Acute Lymphoblastic Leukemia

Journal

PEDIATRIC BLOOD & CANCER
Volume 61, Issue 6, Pages 1017-1022

Publisher

WILEY
DOI: 10.1002/pbc.24951

Keywords

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

Funding

  1. European Society for Pediatric Infectious Diseases (ESPID)

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BackgroundWe 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). ProcedureMBL2 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. ResultsForty-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). ConclusionsMBL2 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. Pediatr Blood Cancer 2014;61:1017-1022. (c) 2014 Wiley Periodicals, Inc.

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