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Published on: November 21, 2018
Deficiency of mannose-binding lectin and burden of infection in children with malignancy: a prospective study
1Immunobiology Unit, Institute of Child Health, 30 Guilford Street, WC1N 1EH, London, UK.
Insights
Mannose-binding lectin (MBL) deficiency prolongs febrile neutropenia in children with cancer. This suggests MBL infusions may help manage chemotherapy complications in pediatric oncology patients.
Area of Science:
- Immunology
- Pediatric Oncology
- Infectious Diseases
Background:
- Infection is a significant cause of mortality in pediatric cancer patients.
- Mannose-binding lectin (MBL) is crucial for innate immunity, and MBL deficiency increases infection susceptibility.
- This study examines MBL's role in infectious complications during childhood cancer treatment.
Purpose of the Study:
- To investigate the impact of mannose-binding lectin (MBL) on infectious complications in children undergoing cancer treatment.
- To correlate MBL levels and genotype with the incidence and duration of febrile neutropenia.
Main Methods:
- 100 children receiving chemotherapy for malignancy were enrolled.
- Febrile neutropenic episodes were monitored for frequency, duration, and cause.
- MBL genotype, phenotype, and serial concentrations were determined and correlated with clinical data.
Main Results:
- MBL concentrations increased in wild-type patients during febrile neutropenia, but not in those with MBL mutations.
- Patients with MBL mutations experienced twice the duration of febrile neutropenia compared to wild-type.
- Lower MBL concentrations at diagnosis correlated with more days of febrile neutropenia.
Conclusions:
- MBL deficiency significantly influences the duration of febrile neutropenic episodes in pediatric cancer patients.
- MBL infusions are a potential therapeutic strategy for managing chemotherapy-induced complications.
- Further research into MBL supplementation could improve outcomes for immunocompromised children.
Background:
Infection is a major cause of morbidity and mortality in children with malignancy. Individuals with serum deficient in mannose-binding lectin (MBL)-an important component of the innate immune system-are more susceptible to infection than those with adequate concentrations. In this study, we investigated the capacity of this protein to influence infectious complications in children undergoing treatment for malignancy.
Methods:
We enrolled 100 children receiving chemotherapy for malignancy at a children's hospital in London, UK. The frequency, duration, and causes of febrile neutropenic episodes were recorded, and MBL genotype and phenotype were determined by heteroduplex analysis and ELISAs, respectively. Serial MBL concentrations were also measured in patients during febrile episodes, and the results correlated with the MBL genotype (A/A indicating wild type, O/O indicating homozygous for MBL structural-gene mutations, and A/O indicating heterozygous for such mutations).
Findings:
In the A/A patients, MBL concentrations almost doubled by day 7 of the febrile neutropenic episode before declining by day 14 (p=0.004). By contrast, in patients with MBL mutations, concentrations did not alter significantly during the neutropenic episode. In the 6 months after initial diagnosis, most patients had at least one febrile neutropenic episode, but the median duration in patients with MBL mutations was twice as long as that in children with the wildtype genotype (20.5 days vs 10.0 days; p=0.014). Individuals with the lowest serum MBL concentrations at the time of diagnosis (<1000 microg/L) had a higher median number of days of febrile neutropenia than did individuals with higher concentrations of MBL (p=0.012).
Interpretation:
MBL deficiency seems to have an important influence on the duration of febrile neutropenic episodes in children with malignancy. This finding suggests that MBL infusions could represent a new therapeutic approach which would aid the management of chemotherapy-induced complications in this population of children.
