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Chen et al. Rare Dis Orphan Drugs J 2022;1:15 Rare Disease and
DOI: 10.20517/rdodj.2022.18
Orphan Drugs Journal

Review Open Access

Targeting neutrophil serine proteinases in alpha-1
antitrypsin deficiency

1
Celine H. Chen , Robert A. Stockley 1,2
1
Birmingham Acute Care Research (BACR) Group, Institute of Inflammation and Ageing, Queen Elizabeth Hospital Birmingham,
University of Birmingham, Birmingham B15 2GW, UK.
2
Department of Sleep and Lung Function, Queen Elizabeth Hospital Birmingham, Birmingham B15 2GW, UK.
Correspondence to: Prof. Robert A. Stockley, Department of Sleep and Lung Function, Queen Elizabeth Hospital Birmingham,
Mendelsohn way, Birmingham B15 2GW, UK. E-mail: R.A.Stockley@bham.ac.uk

How to cite this article: Chen CH, Stockley RA. Targeting neutrophil serine proteinases in alpha-1 antitrypsin deficiency. Rare Dis
Orphan Drugs J 2022;1:15. https://dx.doi.org/10.20517/rdodj.2022.18

Received: 11 Oct 2022 First Decision: 10 Nov 2022 Revised: 28 Nov 2022 Accepted: 7 Dec 2022 Published: 9 Dec 2022
Academic Editors: Brice Korkmaz, Daniel Scherman Copy Editor: Ying Han Production Editor: Ying Han

Abstract
Alpha-1 antitrypsin (AAT) is the most abundant irreversible serine proteinase inhibitor in the circulation and plays
a major role in protecting lung tissue against destruction from neutrophil serine proteinases. Genetic mutation of
AAT leads to reduced circulating levels and AAT deficiency (AATD) which is associated with an increased risk of
developing emphysema. This observation suggests that the balance between AAT and neutrophil serine proteinase
is crucial in maintaining tissue homoeostasis. In AATD, the overexuberant proteinase activity resulting from
inadequate AAT control creates a self-perpetuating inflammatory cycle, driving progressive tissue injury. Re-
establishing this physiological balance is therefore critical for preserving lung architecture, function, and abrogating
disease progression.

Several avenues within this pathophysiological pathway are being explored. This chapter addresses the
pathophysiological process, current treatments targeting the pathway, and alternative approaches within the
pathway that can potentially mitigate proteinase imbalance.

Keywords: Alpha-1 antitrypsin deficiency, neutrophil serine proteinase, treatment targets, emphysema, rare
disease

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
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