Defects in neutrophil granule mobilization and bactericidal activity in familial hemophagocytic lymphohistiocytosis type 5 (FHL-5) syndrome caused by STXBP2/Munc18-2 mutations

Xi Wen Zhao, Roel P Gazendam, Agata Drewniak, Michel van Houdt, Anton T J Tool, John L van Hamme, Iwan Kustiawan, Alexander B Meijer, Hans Janssen, David G Russell, Lisette van de Corput, Kiki Tesselaar, Jaap J Boelens, Ingrid Kuhnle, Jutte Van Der Werff Ten Bosch, Taco W Kuijpers, Timo K van den Berg

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36 Citations (Scopus)


Familial hemophagocytic lymphohistiocytosis (FHL) is caused by genetic defects in cytotoxic granule components or their fusion machinery, leading to impaired natural killer cell and/or T lymphocyte degranulation and/or cytotoxicity. This may accumulate into a life-threatening condition known as macrophage activation syndrome. STXBP2, also known as MUNC18-2, has recently been identified as the disease-causing gene in FHL type 5 (FHL-5). A role for STXBP2 in neutrophils, and for neutrophils in FHL in general, has not been documented thus far. Here, we report that FHL-5 neutrophils have a profound defect in granule mobilization, resulting in inadequate bacterial killing, in particular, of gram-negative Escherichia coli, but not of Staphylococcus aureus, which rather depends on intact reduced NAD phosphate oxidase activity. This impairment of bacterial killing may contribute to the apparent susceptibility to gastrointestinal tract inflammation in patients with FHL-5.

Original languageEnglish
Pages (from-to)109-11
Number of pages3
Issue number1
Publication statusPublished - 4 Jul 2013


  • Cell Degranulation/genetics
  • Cytoplasmic Granules/metabolism
  • Escherichia coli Infections/genetics
  • Escherichia coli/immunology
  • Female
  • Gastroenteritis/genetics
  • Genetic Predisposition to Disease
  • Humans
  • Killer Cells, Natural/immunology
  • Lymphohistiocytosis, Hemophagocytic/genetics
  • Male
  • Munc18 Proteins/genetics
  • Neutrophils/immunology
  • Staphylococcal Infections/genetics
  • Staphylococcus aureus/immunology

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