Neutrophil Elastase Defects in Congenital Neutropenia

Front Immunol. 2021 Apr 22:12:653932. doi: 10.3389/fimmu.2021.653932. eCollection 2021.


Severe congenital neutropenia (SCN) is a rare hematological condition with heterogenous genetic background. Neutrophil elastase (NE) encoded by ELANE gene is mutated in over half of the SCN cases. The role of NE defects in myelocytes maturation arrest in bone marrow is widely investigated; however, the mechanism underlying this phenomenon has still remained unclear. In this review, we sum up the studies exploring mechanisms of neutrophil deficiency, biological role of NE in neutrophil and the effects of ELANE mutation and neutropenia pathogenesis. We also explain the hypotheses presented so far and summarize options of neutropenia therapy.

Keywords: ELANE mutations; cyclic neutropenia; mislocalization; mistrafficking; neutrophil elastase; severe congenital neutropenia; unfolded protein response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Congenital Bone Marrow Failure Syndromes / diagnosis*
  • Congenital Bone Marrow Failure Syndromes / genetics*
  • Gene Expression Regulation
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Leukocyte Elastase / chemistry
  • Leukocyte Elastase / deficiency*
  • Leukocyte Elastase / genetics
  • Leukocyte Elastase / metabolism
  • Mutation
  • Neutropenia / congenital*
  • Neutropenia / diagnosis
  • Neutropenia / genetics
  • Neutrophils / enzymology*
  • Protein Processing, Post-Translational
  • Protein Transport
  • Signal Transduction
  • Structure-Activity Relationship


  • Leukocyte Elastase

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3