Email this article POTENTIAL PROGNOSTIC MARKERS FOR ASSESSING AUTOIMMUNE NATURE ADVERSE EVENTS RISK IN PATIENTS UNDERGOING THERAPY FOR MALIGNANT NEOPLASMS WITH CHECKPOINT INHIBITORS
- Authors: Khizha V.V.1, Kozlova D.I.2, Klyaus N.A.3, Kuzin S.O.4, Sholokhov G.V.4, Khaimanova D.G.4, Ballyzek M.F.5
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Affiliations:
- Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
- SECHENOV INSTITUTE OF EVOLUTIONARY PHYSIOLOGY AND BIOCHEMISTRY RUSSIAN ACADEMY OF SCIENCES Saint-Petersburg Clinical Hospital of the Russian Academy of Sciences
- Federal State Budgetary Institution “V.A. Almazov National Medical Research Center” of the Ministry of Health of the Russian Federation
- Saint-Petersburg Clinical Hospital of the Russian Academy of Sciences
- St. Petersburg State University
- Section: Original research
- Published: 20.12.2024
- URL: https://journals.eco-vector.com/MAJ/article/view/637360
- DOI: https://doi.org/10.17816/MAJ637360
- ID: 637360
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Abstract
Cases of adverse autoimmune nature events are being registered increasingly against the background of the highly effective various malignant diseases types treatment drugs based on checkpoint inhibitors usage. In this regard, the issue of finding and introducing into clinical practice markers that allow identifying patients at risk is urgent. Timely diagnostics can help to conduct preliminary preparation and maintenance therapy to reduce the likelihood of such complications and maintaining the possibility of the most effective methods of oncology treatment further usage.
AIM: to identify a list of autoimmune adverse events development risk assessment markers under checkpoint inhibitors usage, based on the characteristics of patients' cytokine profiles.
MATERIALS AND METHODS: The study was conducted on the biomaterial (blood plasma) of patients with malignant neoplasms (n=21) undergoing therapy with drugs based on checkpoint inhibitors. Patients were divided into 2 groups: 1 - those who received autoimmune nature adverse events (n=6), 2 - without such complications (n=15). The wide cytokines range content study was carried out dynamically with an interval of 2-2.5 weeks, where the starting point was the day preceding the induction of therapy, and the end point was 85 - 95 days after it. The normality of the data distribution was judged by the Shapiro-Wilk criterion, pairwise comparison of samples was performed using the Mann-Whitney criterion, the significance level was adjusted using the a posteriori Sidak criterion.
RESULTS: It was shown that with the development of autoimmune nature adverse events against the background of therapy of malignant neoplasms with checkpoint inhibitors, the content of both polarizing and secreted T-helpers 1 and 17 types cytokines increases, indicating a typical for autoimmune pathologies T-helpers subpopulations balance shift. Interleukin 12-p70, -15 and TGF-β have the highest sensitivity and specificity for assessing the risk of autoimmune nature adverse events in patients who are planned to undergo therapy using checkpoint inhibitors.
CONCLUSION: The conducted study for the first time allowed to demonstrate the possibility of identifying a predisposition to the autoimmune nature adverse reactions development before treatment of malignant neoplasms with checkpoint inhibitors.
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About the authors
Vitaliy V. Khizha
Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Email: khizhaspb@gmail.com
ORCID iD: 0000-0003-4967-472X
SPIN-code: 7187-7610
Scopus Author ID: 57217492710
Junior Research Associate of the Laboratory of the Comparative Physiology and Pathology of the CNS
Russian Federation, 44 Thorez avenue, Saint Petersburg, Russia, 194223.Daria Igorevna Kozlova
SECHENOV INSTITUTE OF EVOLUTIONARY PHYSIOLOGY AND BIOCHEMISTRY RUSSIAN ACADEMY OF SCIENCESSaint-Petersburg Clinical Hospital of the Russian Academy of Sciences
Author for correspondence.
Email: di.kozlova.official@gmail.com
ORCID iD: 0000-0003-1767-2754
SPIN-code: 2041-5544
Scopus Author ID: 56998634500
ResearcherId: Q-1916-2017
PhD in Biology, Leading Researcher, Laboratory of Comparative Physiology andPathology of the CNS, head of the Autoimmune and autoinflammation human diseases
investigations scientificand practical research group
Russian Federation, 44 Thorez avenue, Saint Petersburg, Russia, 194223. 72 Thorez avenue, Saint Petersburg, Russia, 194017.
Nataliya Andreevna Klyaus
Federal State Budgetary Institution “V.A. Almazov National Medical Research Center” of the Ministry of Health of the Russian Federation
Email: klyausn@gmail.com
ORCID iD: 0000-0002-8955-7088
SPIN-code: 5521-9432
Scopus Author ID: 57194064031
ResearcherId: AAL-8881-2020
Junior researcher, research laboratory of rheumatology and immunopathology
Russian Federation, 197341, Russia, Saint Petersburg, Akkuratova st., 2.Sergey Olegovich Kuzin
Saint-Petersburg Clinical Hospital of the Russian Academy of Sciences
Email: dr.kuzin@bk.ru
ORCID iD: 0000-0002-0524-6582
SPIN-code: 2017-7960
Scopus Author ID: 58369416900
oncologist
Russian Federation, 72 Thorez avenue, Saint Petersburg, Russia, 194017.Georgy Vladimirovich Sholokhov
Saint-Petersburg Clinical Hospital of the Russian Academy of Sciences
Email: Doctor.Sholokhov@yandex.ru
ORCID iD: 0009-0003-8453-6047
SPIN-code: 2345-7215
Scopus Author ID: 59314198700
endocrinologist
Russian Federation, 72 Thorez avenue, Saint Petersburg, Russia, 194017.Dzerasa Georgievna Khaimanova
Saint-Petersburg Clinical Hospital of the Russian Academy of Sciences
Email: dze4188@yandex.ru
ORCID iD: 0000-0002-0700-208X
M.D., cardiologist
Russian Federation, 72 Thorez avenue, Saint Petersburg, Russia, 194017.Marina Feliksovna Ballyzek
St. Petersburg State University
Email: marina.ballyzek@mail.ru
ORCID iD: 0000-0003-3223-0241
SPIN-code: 2588-3944
Scopus Author ID: 55941807600
Professor, Doctor of Sciences in Medicine, Professor of the Department of Faculty Therapy
Russian Federation, 199034, Russia, Saint Petersburg, Universitetskaya emb., 7/9.References
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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).