Some Aspects of Mast Cells Carboxypeptidase A3 Participation in the Pathogenesis of COVID-19

Andrey V. Budnevsky, Sergey N. Avdeev, Evgeniy S. Ovsyannikov, Nadezhda G. Alekseeva, Victoria V. Shishkina, Inessa A. Savushkina, Inna M. Perveeva, Sofia N. Feigelman, Avag G. Kitoyan, Valeria R. Drobysheva

International Journal of Biomedicine. 2023;13(4):301-305.
DOI: 10.21103/Article13(4)_OA11
Originally published December 5, 2023


Background: This study aimed to determine the involvement of carboxypeptidase A3 (CPA3) in developing lung damage in patients with COVID-19.
Methods and Results: The study included samples of autopsy material from the lungs of patients who died as a result of severe COVID-19 (the main group [MG] and persons who died from external causes (the control group [CG]). Immunohistochemical staining for CPA3 was carried out. A quantitative study of CPA3-positive mast cells (MCs) and the degree of their degranulation was carried out using a ×40 objective lens with an analysis of ≥50 fields of view with further conversion to 1 mm².
Significant representation of CPA3-positive MCs per 1 mm2 of CPA3-positive MCs, CPA3-positive MCs with signs of degranulation (SD), and co-adjacent MCs was found in the MG compared to the CG (P=0.01 in all cases). In the main group, positive correlations were identified between the total number of CPA3-positive MCs, CPA3-positive MCs with SD and the blood hemoglobin level shortly before death (r=0.491 [P=0.008] and r=0.521 [P=0.004], respectively). Co-adjacent CPA3-positive MCs were negatively correlated with blood eosinophils at the beginning of hospitalization (r=-0.420 [P=0.023]). Also, the number of separately lying, CPA3-positive MCs negatively correlated with the blood monocyte shortly before death (r=-0.384 [P=0.044]). A positive correlation was established between the total number of CPA3-positive MCs, CPA3-positive MCs with SD, and adjacent CPA3-positive MCs with total blood protein in patients at the beginning of hospitalization (r=0.431 [P=0.020], r=0.449 [P=0.015] and r=0.456 [P=0.013], respectively). In addition, the study demonstrated a positive correlation between CPA3-positive MCs with SD and the total number of CPA3-positive MCs with blood aPTT levels (r=0.304 [P=0.045] and r=0.375 [P=0.045], respectively). A negative correlation was also found between the total number of CPA3-positive MCs and the blood INR level (r=-0.812 [P=0.050]). Finally, in patients at the beginning of hospitalization, a negative correlation was found between CPA3-positive MCs with SD, CPA3-positive MCs without SD, separately located CPA3-positive MCs, adjacent CPA3-positive MCs, and the total number of CPA3-positive MCs with blood amylase (r=-0.550 [P=0.002], r=-0.452 [P=0.045], r=-0.485 [P=0.030], r=-0.622 [P=0.008], and r=-0.590 [P=0.006], respectively).
Conclusion: Our study identifies the potential involvement of CPA3 in the pathogenesis of severe COVID-19. However, many aspects of its participation remain unclear and require further study.

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Received October 17, 2023.
Accepted November 25, 2023.
©2023 International Medical Research and Development Corporation.