Background: Myeloperoxidase (MPO) is a heme enzyme predominantly produced and released by activated polymorphonuclear neutrophils (PMN), which plays an important role in microbial killing and host immune responses. MPO has gained increasing attention as a local mediator of tissue damage and a contributor of cardiovascular inflammatory diseases. Hence, current evidence suggests MPO-deficiency to be vasoprotective. However, hereditary forms of MPO deficiency need to be differentiated from transient forms secondary to conditions affecting the immune system.

Aims: To investigate prevalence and causes of hereditary and secondary MPO deficiency in a patient collective of 11 608 patients, hospitalized between February 2018 and January 2019 at the University Hospital Cologne.

Methods and results: A total of 11 608 patients were scrutinized for MPO activity by MPXI-Score using the ADVIA 2120i hematology-system. 282 patients with low MPO activity (MPXI ≤ -18) were originally identified. After three years, MPO enzyme activity of 73 individuals was redetermined by nitric oxide (NO) redoxpotential measurements and tetramethylbenzidine (TMB) assays. N=44 (60%) patients showed persistent MPO-deficiency (MPO^-) while n=29 patients (40%) regained MPO activity (MPO⁺), thus being defined as transiently deficient. While low MPO enzyme-activity of MPO^- individuals correlated with low MPXI-Scores during the primary visit (p=0.04), MPO-enzyme activity of MPO⁺ patients were unstable over time, more divers and did not correlate with the results of the original MPXI-examination (p=0.88). For all following mechanistical analyses, MPO^- and MPO⁺ patients were matched with n=10 MPO-competent controls (MPO^C+) based on gender, age, HbA1c, BMI, LDL and HDL cholesterol, smoking status and hypertension. Control individuals showed a significantly higher MPO-enzyme activity compared to MPO^- patients (p=0.01) and did not differ from MPO⁺ patients (p=0.49). To detect MPO protein-expression in PMNs, immunoblotting and ELISAs were performed. Herein, MPO^- patients showed a significantly lower MPO protein-expression compared to MPO⁺ patients (p=0.02). Within the MPO^- group, lower MPO-enzyme activity correlated significantly with lower MPO protein-expression (p=0.01). Currently smoking MPO⁺ patients or MPO⁺ patients with an underlying chronic inflammatory disease showed a significantly increased MPO-enzyme activity (p=0.03; p=0,04). In contrast, MPO-enzyme activity of MPO^- patients were not affected by smoking or chronic inflammation (p=0.60; p=0.86).

Conclusion: Primary MPO-deficiency is characterized by persistent low MPO-enzyme activity and MPO-protein expression. In contrast, PMN with an antecedent secondary/transient MPO-deficiency do not differ from MPO-competent PMN and can increase MPO-enzyme activity during inflammatory events. Characterization and access of a MPO- patient collective will help to understand fundamental mechanistics of PMN activity and allow to translate preclinical findings of MPO-deficiency being protective against cardiovascular diseases into a human setting. Considering the important role of MPO as a local mediator of tissue damage and contributor to vascular inflammatory diseases, MPO-deficiency in the context of chronic inflammation might furthermore reduce an overactivation of host immune response and protect vulnerable patient collectives.