title: Deficiency of mannose-binding lectin-associated serine protease-2 associated with increased risk of fever and neutropenia in pediatric cancer patients.
abstract: BACKGROUND
  Mannose-binding lectin-associated serine protease-2 (MASP-2) is an essential component of the lectin pathway of complement activation. MASP-2 deficiency is common because of genetic polymorphisms, but its impact on susceptibility to infection is largely unknown. The aim of the present study was to determine whether children with cancer and MASP-2 deficiency develop more frequent or more severe episodes of fever and severe chemotherapy-induced neutropenia (FN).
  
  
  METHODS
  Serum MASP-2 was measured by enzyme-linked immunosorbent assay at the time of diagnosis in children treated with chemotherapy for cancer. Association of FN episodes with MASP-2 concentration was analyzed using Poisson regression accounting for chemotherapy intensity and duration.
  
  
  RESULTS
  Median MASP-2 in 94 children was 527 ng/mL (interquartile range, 367-686). Nine (10%) children had MASP-2 deficiency (<200 ng/mL). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded. MASP-2 deficient children had a significantly increased risk of developing FN (multivariate risk ratio, 2.08; 95% confidence interval, 1.31-3.21; P = 0.002), translating into significantly prolonged cumulative duration of hospitalization and of intravenous antimicrobial therapy. They experienced significantly more episodes of FN without a microbiologically defined etiology, and there was a trend toward more frequent episodes of FN with bacteremia.
  
  
  CONCLUSIONS
  In this study, MASP-2 deficiency was associated with an increased risk of FN in children treated with chemotherapy for cancer. MASP-2 deficiency represents a novel risk factor for chemotherapy-related infections.
authors.affiliation: Department of Pediatrics, University of Bern, Bern, Switzerland.
authors.forename: Luregn J
authors.initials: LJ
authors.lastname: Schlapbach
authors.forename: Christoph
authors.initials: C
authors.lastname: Aebi
authors.forename: Margrith
authors.initials: M
authors.lastname: Otth
authors.forename: Kurt
authors.initials: K
authors.lastname: Leibundgut
authors.forename: Andreas
authors.initials: A
authors.lastname: Hirt
authors.forename: Roland A
authors.initials: RA
authors.lastname: Ammann
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D001424:Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D002648:Child; D002675:Child, Preschool; D004198:Disease Susceptibility; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000453:epidemiology*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000172:deficiency* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology*; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases