ANTIGENPRESENTING SUBSETS OF NEUTROPHILIC GRANULOCYTES AS A DIAGNOSTIC MARKER OF THE DYNAMICS OF CLINICAL EFFECTIVENESS OF IMMUNOMODULATORY THERAPY WITH SYNTHETIC THYMIC HEXAPEPTIDE IN CHILDREN WITH ACUTE HEMATOGENOUS OSTEOMYELITIS
https://doi.org/10.15789/1563-0625-ASO-3434
Abstract
The multifunctionality of neutrophilic granulocytes (NG) is associated with the presence of various subsets and phenotypes. Previously, in children with severe purulent inflammatory diseases, a correlation was found between the severity of disease and the number of CD66b+CD16+CD33+HLA-DR+NG (APC-NG) subset. Thus, the determination of the APC-NG subset can serve as a valuable diagnostic tool and an indicator of the effectiveness of complex therapy in severe purulent-inflammatory diseases.
Goal: to assess the dynamic changes in APC-NG level in children with AHO in comparison with the dynamics of indicators of clinical effectiveness during immunomodulatory therapy with a synthetic thymic hexapeptide (HP).
Materials and methods. The study group (SG) included children aged 10-15 years with AHO (n=15), the comparison group (CG) consisted of 13 conditionally healthy children. In the peripheral blood (PB) of children, the content of NG expressing CD66b, CD16, CD33, HLA-DR (FC500, Beckman Coulter) and the expression density of these molecules was evaluated. The PB was collected before surgery, on the 10th day of therapy, and before discharge. The immunological parameters of children with CG were studied once.
Results: It was found that the amount of APC-NG, which was increased by 18 times in SG before treatment, decreased by 1,9 times on the 10th day after the beginning of treatment and by 3,8 times by the time of discharge (20-25th day). However, the content of APC-NG after treatment did not reach the CG indicators. In addition, a decrease in the number of APC-NG correlated with positive clinical dynamics: there was an earlier regression of general and local symptoms. A delay in the positive changes of APC-NG was observed in the absence of clinical effectiveness, which required a revision of therapeutic tactics and the need to change antibacterial therapy.
Conclusion: The study demonstrated the high clinical efficacy of HP in the complex treatment of children with AHO and the possibility of using the content of the APC-NG subset as a diagnostic marker for monitoring efficacy of postoperative treatment of children with AHO. This marker can also serve as a tool that allows for timely adjustment of the treatment of patients with AHO.
Keywords
About the Authors
I. V. NesterovaRussian Federation
Doctor of Medical Sciences (MD), Professor, aChief Researcher, Department of Clinical and Experimental Immunology and Molecular Biology, Central Scientific Research Laboratory,
bProfessor of the Department of Clinical Immunology, Allergology and Adaptology Faculty of Continuing Medical Education of the Medical Institute
Competing Interests:
The author declares that there is no conflict of interest
G. A. Chudilova
Russian Federation
Doctor of Biological Sciences, Associate Professor, Head of the Department of Clinical and Experimental Immunology and Molecular Biology of the Central Research Laboratory, Professor of the Department of Clinical Immunology, Allergology and Laboratory Diagnostics
Competing Interests:
The author declares that there is no conflict of interest
N. K. Barova
Russian Federation
PhD (Medical Sciences), Associate Professor,
аHead of the Department of Surgical Diseases of Childhood,
bHead, Surgical Department No. 1
Competing Interests:
The author declares that there is no conflict of interest
A. D. Safontseva
Russian Federation
Postgraduate Student, Department of Clinical Immunology, Allergology and Laboratory Diagnostics, Junior Researcher of the Department of Clinical and Experimental Immunology and Molecular Biology of the Central Scientific Research Laboratory
Competing Interests:
The author declares that there is no conflict of interest
E. A. Poezzhaev
Russian Federation
Postgraduate Student, Department of Clinical Immunology, Allergology and Laboratory Diagnostics, Junior Researcher of the Department of Clinical and Experimental Immunology and Molecular Biology of the Central Scientific Research Laboratory
Competing Interests:
The author declares that there is no conflict of interest
S. V. Kovaleva
Russian Federation
Doctor of Medical Sciences (MD), Associate Professor, Senior Researcher of the Department of Clinical and Experimental Immunology and Molecular Biology of the Central Scientific Research Laboratory, Professor of the Department of Clinical Immunology, Allergology and Laboratory Diagnostics
Competing Interests:
The author declares that there is no conflict of interest
V. N. Chapurina
Russian Federation
PhD (Medical Sciences), Associate Professor of the Department of Clinical Immunology, Allergology and Laboratory Diagnostics, Senior Researcher of the Department of Clinical and Experimental Immunology and Molecular Biology of the Central Scientific Research Laboratory
Competing Interests:
The author declares that there is no conflict of interest
E. A. Chicherev
Russian Federation
Pediatric oncologist at the Oncology department
Competing Interests:
The author declares that there is no conflict of interest
Yu. V. Teterin
Russian Federation
Assistant of the Department of Clinical Immunology, Allergology and Laboratory Diagnostics
Competing Interests:
The author declares that there is no conflict of interest
L. V. Lomtatidze
Russian Federation
PhD in Biology, senior researcher of the department of clinical and experimental immunology and molecular biology of the Central Scientific Research Laboratory, Associate Professor of the Department of Clinical Immunology, Allergology and Laboratory Diagnostics
Competing Interests:
The author declares that there is no conflict of interest
D. E. Lyagusha
Russian Federation
pediatrician of the surgical department No. 1
Competing Interests:
The author declares that there is no conflict of interest
References
1. Vorobjeva N.V. Neutrophils are atypical antigen-presenting cells. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya, 2023, Vol. 78 (2), pp. 55-63. 10.55959/MSU0137-0952-16-78-2-8
2. Dolgushin I.I., Mezentseva E.A., Savochkina A.Yu., Kuznetsova E.K. Neutrophil as a multifunctional relay in immune system // Infektsiya i immunitet, 2019, Vol. 9, no. 1, pp. 9–38. 10.15789/2220-7619-2019-1-9-38
3. Nesterova I.V., Kolesnikova N.V., Chudilova G.A., Lomtatidze L.V., Kovaleva S.V., Evglevsky A.A., Nguyen T.D.L. The new look at neutrophilic granulocytes: rethinking old dogmas. Part 2. Russian Journal of Infection and Immunity, 2018, Vol. 8, no. 1, pp. 7–18. 10.15789/2220-7619-2018-1-7-18
4. Nesterova I.V., Chudilova G.A., Teterin Yu.V., Chapurina V.N., Safontseva A.D., Kovaleva S.V., Lomtatidze L.V., Lyagusha D.E., Barova N.K., Poyezjayev E.A. Variants of laboratory immunophenotypes of acquired immunodeficiency with predominance of neutrophil granulocyte dysfunctions in children with acute destructive pneumonia complicated by sepsis. Pediatriya. Zhurnal im G.N. Speranskogo, 2025, Vol. 104, no. 2, pp. 49-58. 10.24110/0031-403X-2025-104-2-49-58
5. Potapnev M.P., Hushchyna L.M., Moroz L. Human neutrophils subpopulations and functions heterogeneity in norm and pathology. Immunologiya, 2019, Vol. 40 (5), pp. 84-96. 10.24411/0206-4952-2019-15010.
6. Chudilova G.A., Chicherev E.A., Teterin Yu.V., Chapurina V.N., Tarakanov V.A., Barova N.K., Nesterova I.V. Clinical and immunological efficacy of the immunomodulating hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosylarginine in the complex postoperative treatment of children with acute osteomyelitis. Russian Journal of Immunology, 2023, Vol. 26, no. 4, pp. 679-688 10.46235/1028-7221-13763-CAI
7. Beyrau M., Bodkin J. V., Nourshargh S. Neutrophil heterogeneity in health and disease: a revitalized avenue in inflammation and immunity. Open Biol, 2012, Vol. 2, pp.120134. 10.1098/rsob.120134
8. Chatfield S.M., Thieblemont N., Witko-Sarsat V. Expanding neutrophil horizonts: new concepts in inflammation. J. Innate Immun, 2018, Vol. 10, pp. 422-431. 10.1159/000493101
9. Ericson J.A., Duffau P., Yasuda K., Ortiz-Lopez A., Rothamel K., RifkinI. R., Monach P.A., Imm Gen Consortium. Gene expression during the generation and activation of mouse neutrophils: implication of novel functional and regulatory pathways. PLoS ONE, 2014, Vol. 9 (10), pp. e108553. 10.1371/journal.pone.0108553
10. Forrer P., Palianina D., Stühler C., Kreuzaler M., Roux J., Li J., Schmutz C., Burckhardt D., Franzeck F., Finke D., Schmidt A., Bumann D., Khanna N. Unveiling signaling pathways inducing MHC class II expression in neutrophils. Front Immunol, 2024, Vol. 15, 1444558. 10.3389/fimmu.2024.1444558
11. Greenlee-Wacker M. C. Clearance of apoptotic neutrophils and resolution of inflammation. Immunol. Rev, 2016, Vol. 273, pp.357–370. 10.1111/imr.12453
12. Iking-Konert C., Ostendorf B., Sander O., Jost M., Wagner C., Joosten L., Schneider M., Hänsch G. M. Transdifferentiation of polymorphonuclear neutrophils to dendritic-like cells at the site of inflammation in rheumatoid arthritis: evidence for activation by T cells. Ann Rheum Dis, 2005, Vol. 64, pp. 1436–42. 10.1136/ard.2004.034132
13. Iking-Konert C., Vogt S., Radsak M., Wagner C., Hansch G. M., Andrassy K. Polymorphonuclear neutrophils in Wegener’s granulomatosis acquire characteristics of antigen presenting cells. Kidney Int, 2001, Vol. 60, pp. 2247–2262. 10.1046/j.1523-1755.2001.00068
14. Li Y., Wang W., Yang F., Xu Y., Feng C., Zhao Y. The regulatory roles of neutrophils in adaptive immunity. Cell Commun Signal, 2019, Vol. 17 (1), pp. 147. 10.1186/s12964-019-0471-y
15. Lin A., Loré K. Granulocytes: new members of the antigen-presenting cell family. Front Immunol, 2017, Vol. 8, pp. 1781 10.3389/fimmu.2017.01781
16. Mayadas T.N., Cullere X., Lowell C.A. The multifaceted functions of neutrophils. Annu Rev Pathol, 2014, Vol. 9, pp. 181–218. 10.1146/annurev-pathol-020712-164023
17. Mishalian I., Granot Z., Fridlender Z. G. The diversity of circulating neutrophils in cancer. Immunobiology, 2017, Vol. 222, 82–88. 10.1016/j.imbio.2016.02.001
18. Moffat A., Gwyer Findlay E. Evidence for antigen presentation by human neutrophils.
19. Blood. 2024, Vol. 143 (24), pp. 2455-2463. 10.1182/blood.2023023444
20. Murao A., Aziz M., Wang P. Neutrophil heterogeneity in sepsis: the role of damage-associated molecular patterns. Shock. 2023, Vol. 59(2), pp. 239-246. 10.1097/SHK.0000000000002019
21. Nauseef W. M., Borregaard N. Neutrophils at work. Nat. Immunol, 2014, Vol. 15, pp. 602–611. 10.1038/ni.2921
22. Nesterova I.V., Chudilova G.A., Teterin Yu.V., Chicherev E.A., Chapurina V.N., Mitropanova M.N. Antigen presenting subset of СD66b+CD16+CD33+HLA-DR+ neutrophilic granulocytes in acute osteomyelitis in children: Immunomodulating effects of immunotropic hexapeptide in an in vitro experimental system. Medical Immunology, 2023, Vol. 25 (4), pp. 899-906. 10.15789/1563-0625-APS-2776
23. Netea M. G., Joosten L. A., Latz E., Mills K. H., Natoli G., Stunnenberg H. G., O'Neill L. A., Xavier R.J. Trained immunity: a program of innate immune memory in health and disease. Science, 2016, Vol. 352, pp. aaf1098. 10.1126/science.aaf1098
24. Rosales C. Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?. Front. Physiol, 2018, Vol. 9, pp.113. 10.3389/fphys.2018.00113
25. Scapini P., Cassatella M. A. Social networking of human neutrophils within the immune system. Blood, 2014, Vol. 124, pp. 710–719. 10.1182/blood-2014-03-453217
26. Takashima A., Yao Y. Neutrophil plasticity: acquisition of phenotype and functionality of antigen-presenting cell. J Leukoc Biol, 2015, Vol. 98, pp. 489–96. 10.1189/jlb.1MR1014-502R
27. TecchioC.Cassatella M. A. Neutrophil-derived chemokines on the road to immunity. Semin. Immunol. 2016, Vol. 28, pp. 119–128. 10.1016/j.smim.2016.04.003
28. Tsai C.Y., Hsieh S.C., Liu C.W., Lu C.S., Wu C.H., Liao H.T., Chen M.H., Li K.J., Shen C.Y., Kuo Y.M., Yu C.L. Cross-Talk among Polymorphonuclear Neutrophils, Immune, and Non-Immune Cells via Released Cytokines, Granule Proteins, Microvesicles, and Neutrophil Extracellular Trap Formation: A Novel Concept of Biology and Pathobiology for Neutrophils. Int J Mol Sci, 2021, Vol. 22 (6), pp. 3119. 10.3390/ijms22063119
29. Vono M., Lin A., Norrby-Teglund A., Koup R.A., Liang F., Loré K. Neutrophils acquire the capacity for antigen presentation to memory CD4+ T cells in vitro and ex vivo. Blood, 2017, Vol. 129 (14), 1991–2001. 10.1182/blood-2016-10-744441
30. Zhao T., Jiang Q., Li W., Wang Y., Zou Y., Chai X., Yuan Z., Ma L., Yu R., Deng T., Yu C., Wang T. Antigen-presenting cell-like neutrophils foster T cell response in hyperlipidemic patients and atherosclerotic mice. Front Immunol, 2022, Vol. 13, pp. 851713. 10.3389/fimmu.2022.851713
Supplementary files
|
1. 3434 | |
| Subject | ||
| Type | Other | |
Download
(280KB)
|
Indexing metadata ▾ | |
Review
For citations:
Nesterova I.V., Chudilova G.A., Barova N.K., Safontseva A.D., Poezzhaev E.A., Kovaleva S.V., Chapurina V.N., Chicherev E.A., Teterin Yu.V., Lomtatidze L.V., Lyagusha D.E. ANTIGENPRESENTING SUBSETS OF NEUTROPHILIC GRANULOCYTES AS A DIAGNOSTIC MARKER OF THE DYNAMICS OF CLINICAL EFFECTIVENESS OF IMMUNOMODULATORY THERAPY WITH SYNTHETIC THYMIC HEXAPEPTIDE IN CHILDREN WITH ACUTE HEMATOGENOUS OSTEOMYELITIS. Medical Immunology (Russia). (In Russ.) https://doi.org/10.15789/1563-0625-ASO-3434
JATS XML





































