Comparative analysis of myeloperoxidase deficiency in humans and mice: Conserved and species-specific effects on neutrophil biology
7 affiliations
- 1Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- 2Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- 3Faculty of Medicine and University Hospital Cologne, Polyclinic for Operative Dentistry and Periodontology, University of Cologne, Cologne, Germany
- 4Heart Center, Department of Cardiac Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
- 5Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
- 6Institute of Clinical Chemistry, University of Cologne, Cologne, Germany
- 7Heart Center, Department of Cardiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Corresponding author. Department of Internal Medicine III Heart Center University Hospital Cologne LFI Building, Floor 4 R 62 Kerpener Str. 62, 50937, Cologne, Germany.
Abstract
Background: Myeloperoxidase (MPO), a heme-containing enzyme released by activated polymorphonuclear neutrophils (PMNs) represents a key mediator of inflammation-driven cardiovascular disease, positioning MPO as a promising therapeutic target. However, substantial interspecies differences between murine and human neutrophil biology challenge the translation of preclinical findings from rodent studies into patients. Methods: 11,608 patients were screened for MPO deficiency using the ADVIA 2120i system. 282 individuals exhibited a reduced MPO activity. 56 patients were eligible, consented to be enrolled and were compared to 20 control patients. MPO levels and activity were measured by enzyme-linked immunosorbent assay (ELISA), immunoblotting, a tetramethylbenzidin (TMB)-based peroxidase and nitric oxide (NO)-consumption assay. For cross-species analysis, shotgun proteomics, Gene Ontology (GO) and REACTOME pathway enrichment analyses were conducted on bone marrow derived PMNs from Mpo −/− mice and human MPO-deficient PMNs. Results: Patients with persistent (MPO low , n = 12) and transient (MPO rec , n = 44) MPO deficiency were identified. MPO low individuals showed significantly decreased neutrophil MPO concentrations, enzymatic activity, and plasma MPO levels. Proteomic profiling revealed substantial overlap in altered biological processes across both species. Species-specific enrichments included humoral immunity, complement activation, and coagulation in humans, phagocytosis, chemotaxis, and transcriptional regulation in mice. These differences have been reported alongside distinct signaling patterns, with predominance of Mitogen-activated protein (MAP)-kinase and cytokine activity in humans, and Ras homolog family (Rho)-GTPase pathways in mice. Conclusion: MPO deficiency leads to broadly conserved alterations in neutrophil immune and stress responses across humans and mice. However, similar functional outcomes may involve different signaling pathways in each species contributing to divergent phenotypes in disease models. These findings underscore species-specific mechanisms in MPO-related neutrophil biology and highlight critical considerations for translating MPO-targeted therapies from animal models to human disease.
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BibTeX
@article{ahdab2026comparative,
title = {{Comparative analysis of myeloperoxidase deficiency in humans and mice: Conserved and species-specific effects on neutrophil biology}},
author = {Maysam Ahdab and Henning Guthoff and Nathalie Nix and Sonja Derman and Anna Greta Barbe and Harshal Nemade and Elvina S. Philip and Kezia Singgih and Kathrin Nellessen and Alina Hüttermann and Adnana Paunel-Görgülü and Chris Diekmann and Friedrich F. Hoyer and Patrick Schelemei and Jan-Wilm Lackmann and Stefan Müller and Wibke Johannis and Thomas Streichert and Stephan Baldus and Holger Winkels and Philipp von Stein and Martin Mollenhauer and Alexander Hof},
journal = {Redox Biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104386},
url = {https://doi.org/10.1016/j.redox.2026.104386},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comparative analysis of myeloperoxidase deficiency in humans and mice: Conserved and species-specific effects on neutrophil biology
AU - Maysam Ahdab
AU - Henning Guthoff
AU - Nathalie Nix
AU - Sonja Derman
AU - Anna Greta Barbe
AU - Harshal Nemade
AU - Elvina S. Philip
AU - Kezia Singgih
AU - Kathrin Nellessen
AU - Alina Hüttermann
AU - Adnana Paunel-Görgülü
AU - Chris Diekmann
AU - Friedrich F. Hoyer
AU - Patrick Schelemei
AU - Jan-Wilm Lackmann
AU - Stefan Müller
AU - Wibke Johannis
AU - Thomas Streichert
AU - Stephan Baldus
AU - Holger Winkels
AU - Philipp von Stein
AU - Martin Mollenhauer
AU - Alexander Hof
PY - 2026
DA - 2026/10/30
JO - Redox Biology
DO - 10.1016/j.redox.2026.104386
UR - https://doi.org/10.1016/j.redox.2026.104386
AB - Background: Myeloperoxidase (MPO), a heme-containing enzyme released by activated polymorphonuclear neutrophils (PMNs) represents a key mediator of inflammation-driven cardiovascular disease, positioning MPO as a promising therapeutic target. However, substantial interspecies differences between murine and human neutrophil biology challenge the translation of preclinical findings from rodent studies into patients. Methods: 11,608 patients were screened for MPO deficiency using the ADVIA 2120i system. 282 individuals exhibited a reduced MPO activity. 56 patients were eligible, consented to be enrolled and were compared to 20 control patients. MPO levels and activity were measured by enzyme-linked immunosorbent assay (ELISA), immunoblotting, a tetramethylbenzidin (TMB)-based peroxidase and nitric oxide (NO)-consumption assay. For cross-species analysis, shotgun proteomics, Gene Ontology (GO) and REACTOME pathway enrichment analyses were conducted on bone marrow derived PMNs from Mpo −/− mice and human MPO-deficient PMNs. Results: Patients with persistent (MPO low , n = 12) and transient (MPO rec , n = 44) MPO deficiency were identified. MPO low individuals showed significantly decreased neutrophil MPO concentrations, enzymatic activity, and plasma MPO levels. Proteomic profiling revealed substantial overlap in altered biological processes across both species. Species-specific enrichments included humoral immunity, complement activation, and coagulation in humans, phagocytosis, chemotaxis, and transcriptional regulation in mice. These differences have been reported alongside distinct signaling patterns, with predominance of Mitogen-activated protein (MAP)-kinase and cytokine activity in humans, and Ras homolog family (Rho)-GTPase pathways in mice. Conclusion: MPO deficiency leads to broadly conserved alterations in neutrophil immune and stress responses across humans and mice. However, similar functional outcomes may involve different signaling pathways in each species contributing to divergent phenotypes in disease models. These findings underscore species-specific mechanisms in MPO-related neutrophil biology and highlight critical considerations for translating MPO-targeted therapies from animal models to human disease.
SN - 2213-2317
ER -