DYSREGULATION OF TH17 AND REGULATORY T-CELLS IN NON-LÖFGREN SYNDROME PULMONARY SARCOIDOSIS: A POTENTIAL BIOMARKER FOR DISEASE MANAGEMENT
- Authors: Elgouhari A.S.1, Lazareva N.M.2, Baranova O.P.3, Kudryavtsev I.V.4,3, Ses’ T.P.5, Ilkovich M.M.3, Totolian A.A.6,3
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Affiliations:
- ITMO University, St. Petersburg, Russian Federation.
- Federal State Budgetary Institution Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological Agency - St. Petersburg, Russian Federation.
- First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation.
- Institute of Experimental Medicine
- First St. Petersburg State I. Pavlov Medical University. St. Petersburg, Russian Federation.
- Saint Petersburg Pasteur Institute
- Section: Joint Immunology Forum 2024
- URL: https://rusimmun.ru/jour/article/view/16797
- DOI: https://doi.org/10.46235/1028-7221-16797-DOT
- ID: 16797
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Abstract
Sarcoidosis is a multisystem inflammatory disease of unknown etiology characterized by the formation of non-caseating granulomas, most commonly in the lung tissue. It presents with two main forms: acute and chronic. Patients with chronic sarcoidosis tend to have a less favorable prognosis with a risk of developing lung fibrosis. Sarcoidosis development involves the activation of T cells, which release various chemokines and cytokines that stimulate the inflammatory process. The aim of our study was to investigate the role of the ratio between Th17 and Treg cells in the chronic course of sarcoidosis. We studied peripheral blood plasma samples from patients with chronic sarcoidosis (CS) (n = 101) and healthy individuals (HC) (n = 40). The diagnosis in CS patients was confirmed by histological methods. We determined the levels of Th17 and Treg (% of total lymphocytes) by flow cytometry. The concentration of cytokines (pg/ml) IL-17A and IL-10 was measured by multiplex analysis using Luminex xMap. Correlations between the Th17/Treg ratio and clinical parameters, including serum angiotensin-converting enzyme (sACE) activity level in the peripheral blood, Forced expiratory volume in the first second (FEV1, %), fibrosis manifestations, and extrapulmonary manifestations were analyzed in CS patients. Our analysis revealed elevated levels of Th17 cells (p = 0.028) and decreased Treg levels (p = 0.026) in CS patients compared to healthy controls. This resulted in a significantly increased Th17/Treg ratio (p = 0.003) and IL-17A/IL-10 ratio (p < 0.001) in sarcoidosis patients. Furthermore, the Th17/Treg ratio positively correlated with sACE levels (p=0.018), fibrosis manifestations (p=0.019), and extrapulmonary manifestations (p=0.016), and negatively correlated with FEV1% (p=0.021). Our results indicate an increase in the Th17/Treg ratio, as well as the ratio of their main cytokines in patients with chronic sarcoidosis, which may emphasize their potential role as a diagnostic and prognostic biomarker of disease severity. At the molecular level, the balance between Treg and Th17 cells is maintained by the transcription factors Foxp3 and ROR????t, which regulate the differentiation and function of these cells. Disruption of this balance in patients with chronic sarcoidosis may indicate a possible mechanism for disease progression.
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About the authors
Amro Samir Fawzi Omar Elgouhari
ITMO University, St. Petersburg, Russian Federation.
Email: amr.s.f.o@gmail.com
Student, Faculty of Biotechnologies
Lomonosova St. 9, 191002, St. Petersburg.Natalia Mikhailovna Lazareva
Federal State Budgetary Institution Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological Agency - St. Petersburg, Russian Federation.
Email: nmlazareva@gmail.com
PhD (Medicine), Head of the Clinical Diagnostic Laboratory of Molecular Genetic Research at the Clinic of the Research Center of Cellular and Molecular Pathology
Olga Petrovna Baranova
First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation.
Email: dr_baranova@mail.ru
PhD (Medicine), Research Institute of Interstitial and Orphan Lung Diseases, Associate Professor, Department of Pulmonology
Igor Vladimirovich Kudryavtsev
Institute of Experimental Medicine;First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation.
Email: igorek1981@yandex.ru
PhD (Biology), Head, Laboratory of Immunoregulation, Department of Immunology, Institute of Experimental Medicine; Associate Professor, Department of Immunology, First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation.
Tatiana Pavlovna Ses’
First St. Petersburg State I. Pavlov Medical University. St. Petersburg, Russian Federation.
Email: sestp@mail.ru
PhD, MD (Biology), Professor, Department of Immunology
Mikhail Mikhailovich Ilkovich
First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation.
Email: mihilkovich@yanbex.ru
PhD, MD (Medicine), Professor, Director, Research Institute of Interstitial and Orphan Diseases, Head of the Department of Pulmonology
Areg Artemovich Totolian
Saint Petersburg Pasteur Institute;First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation.
Author for correspondence.
Email: totolian@spbraaci.ru
PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Director, Saint Petersburg Pasteur Institute; Head, Department of Immunology, First St. Petersburg State I. Pavlov Medical University, St. Petersburg, Russian Federation.