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Mazur et al. Rare Dis Orphan Drugs J 2023;2:1 Rare Disease and
DOI: 10.20517/rdodj.2022.12
Orphan Drugs Journal

Review Open Access

Elastase-dependent congenital neutropenia

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Angelika Mazur , Joanna Skrzeczynska-Moncznik , Pawel Majewski , Joanna Cichy
Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow 30-387,
Poland.
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These authors contributed equally to this paper.
Correspondence to: Prof. Joanna Cichy, Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology,
Jagiellonian University, Krakow 30-387, Poland. E-mail: Joanna.Cichy@uj.edu.pl
How to cite this article: Mazur A, Skrzeczynska-Moncznik J, Majewski P, Cichy J. Elastase-dependent congenital neutropenia.
Rare Dis Orphan Drugs J 2023;2:1. https://dx.doi.org/10.20517/rdodj.2022.12
Received: 6 Sep 2022 First Decision: 11 Jan 2023 Revised: 17 Jan 2023 Accepted: 30 Jan 2023 Published: 6 Feb 2023

Academic Editors: Daniel Scherman, Brice Korkmaz Copy Editor: Ying Han Production Editor: Ying Han

Abstract
Congenital neutropenia, which refers to an inherited deficiency in neutrophils, is a rare pathologic condition that
affects approximately 0.0001-0.0009% of the general population. While congenital neutropenia can result from
mutations in approximately 30 genes, its leading cause is gain-of-function mutations in the ELANE gene, which
encodes the neutrophil granule serine protease, neutrophil elastase. This review focuses on established and novel
concepts in the genetic, molecular and cellular mechanisms underlying neutrophil elastase-dependent neutropenia,
and discusses possible new avenues for neutropenia research as well as potential novel treatment options that
target pathogenic elastase variants.

Keywords: Neutropenia, neutrophil elastase, ELANE gene editing, neutrophil elastase inhibitor, secretory leukocyte
protease inhibitor

INTRODUCTION
Congenital neutropenia is a genetic disorder in which there is a lower-than-normal number of neutrophils.
In cases of severe neutropenia, circulating neutrophil counts, which are normally around 1500-8500/μl
blood in healthy human individuals, drop below 500/μl, and in very severe cases, they can be as low as
< 200/μl to close to zero . Since neutrophils play a key role in immune surveillance, mainly against bacteria
[1,2]
and fungi, an inherited deficiency of them predisposes the sufferer to recurrent bacterial, or fungal

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
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adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
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