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


METHODS
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.
Pediatric Hematology Oncology Unit, 2nd Department of Pediatrics, Aristotle University School of Medicine, AHEPA General Hospital, Thessaloniki, Greece; Biochemistry Laboratory, Aristotle University School of Medicine, Thessaloniki, Greece; Biochemistry Laboratory, Department of Chemistry, Aristotle University Faculty of Chemistry, Thessaloniki, Greece; Infectious Disease Unit, 3rd Department of Pediatrics, Aristotle University School of Medicine, Hippokration General Hospital, Thessaloniki, Greece.
Zoe Dorothea
ZD
Pana
Fekri
F
Samarah
Rigini
R
Papi
Charalampos
C
Antachopoulos
Theodotis
T
Papageorgiou
Evangelia
E
Farmaki
Emmanuel
E
Hatzipantelis
Athanassios
A
Tragiannidis
Norma
N
Vavatsi-Christaki
Dimitrios
D
Kyriakidis
Fani
F
Athanassiadou-Piperopoulou
Emmanuel
E
Roilides
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001424:Bacterial Infections / Q000209:etiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D064147:Febrile Neutropenia / Q000139:chemically induced / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D016867:Immunocompromised Host; D007223:Infant; D037102:Lectins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008661:Metabolism, Inborn Errors / Q000150:complications / Q000276:immunology; D011110:Polymorphism, Genetic; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000235:genetics*; D012306:Risk; D000097604:Ficolins
D003062:Codon; D037102:Lectins; D037601:Mannose-Binding Lectin; D000097604:Ficolins; C445619:MBL2 protein, human
B-ALL ;bacterial infections; MBL polymorphisms; ficolin L gene polymorphisms; immunosuppression; pattern recognition receptors