Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients

Sarcoidosis is a multisystemic granulomatous disorder of unknown cause, characterized by formation of immune granulomas in various organs, mainly in lungs. Currently, two main phenotypes of pulmonary sarcoidosis are described, i.e., Lofgren’s syndrome (LS) is an acute form with favorable outcome, an...

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Main Authors: I. V. Kudryavtsev, N. M. Lazareva, O. P. Baranova, M. K. Serebriakova, T. P. Ses’, M. M. Ilkovich, A. A. Totolian
Format: Article
Language:Russian
Published: St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists 2022-07-01
Series:Медицинская иммунология
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Online Access:https://www.mimmun.ru/mimmun/article/view/2468
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author I. V. Kudryavtsev
N. M. Lazareva
O. P. Baranova
M. K. Serebriakova
T. P. Ses’
M. M. Ilkovich
A. A. Totolian
author_facet I. V. Kudryavtsev
N. M. Lazareva
O. P. Baranova
M. K. Serebriakova
T. P. Ses’
M. M. Ilkovich
A. A. Totolian
author_sort I. V. Kudryavtsev
collection DOAJ
description Sarcoidosis is a multisystemic granulomatous disorder of unknown cause, characterized by formation of immune granulomas in various organs, mainly in lungs. Currently, two main phenotypes of pulmonary sarcoidosis are described, i.e., Lofgren’s syndrome (LS) is an acute form with favorable outcome, and non-Lofgren’s syndrome (nLS) is a chronic type of disease with a high risk of pulmonary fibrosis. Our study was aimed to investigate the balance of main “polarized” CD4+ central and effector memory T cells from treatment-naive patients with pulmonary sarcoidosis (LS (n = 19) and nLS (n = 63)) compared to healthy volunteers (HC, n = 48). This marker might be used as immunological markers for predicting severity of this disorder. Multicolor flow cytometry analysis demonstrated that the patients with nLS showed significantly low levels of relative and absolute numbers of CD3+CD4+ lymphocytes if compared to patients with LS and control group (38.94% (31.33-44.24) versus 48.96% (43.34-53.54) and 47.63% (43.82-52.73), p < 0.001 in both cases). Moreover, patients with nLS had reduced frequencies and absolute numbers of “naive”, CM and EM Th cells if compared with healthy controls. Furthermore, the patients with LS showed increased relative and absolute numbers of peripheral blood EM Th cells, capable for migration to peripheral inflamed tissues, when compared with nLS. Finally, patients with LS had increased frequencies and absolute numbers of effector TEMRA Th cells as compared to HC and nLS. Next, significant differences Th1 and Th2 cells frequencies were shown between the patients with nLS and HC (9.64% (7.06-13.65) versus 13.80% (11.24-18.03) with p < 0.001, and 11.96% (9.86-14.78) versus 10.67% (9.13-12.98) with p = 0.048, respectively). But there were no significant differences in the relative numbers of CXCR5-CCR6+Th17 and CXCR5+ follicular T helper cells (Tfh) between the groups. Finally, both groups of patients with pulmonary sarcoidosis contained low proportions of “non-classical” Th17 and DN Th17 cell, but increased levels of DP Th17 cells within total CXCR5-CCR6+ CM Th if compared with HC. Nevertheless, patients with nLS had increased frequency of “classical” Th17 in comparison with healthy controls. A very similar imbalance between different Th17 cell subsets was observed within total CXCR5CCR6+ effector memory Th, that were able to migrate from the bloodstream to the sites of infection, or tissue injury. Taken together, the data suggest that the proportions of Th17 cell subsets in pulmonary sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical practice and these cells could serve as a new therapeutic target.
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spelling doaj.art-7e83a774cb6040d2a4f270116a3d14222024-04-22T13:07:48ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2022-07-0124357358610.15789/1563-0625-PBT-24681555Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patientsI. V. Kudryavtsev0N. M. Lazareva1O. P. Baranova2M. K. Serebriakova3T. P. Ses’4M. M. Ilkovich5A. A. Totolian6First St. Petersburg State I. Pavlov Medical University; Institute of Experimental MedicineFirst St. Petersburg State I. Pavlov Medical UniversityFirst St. Petersburg State I. Pavlov Medical UniversityInstitute of Experimental MedicineFirst St. Petersburg State I. Pavlov Medical UniversityFirst St. Petersburg State I. Pavlov Medical UniversityFirst St. Petersburg State I. Pavlov Medical University; St. Petersburg Pasteur Research Institute of Epidemiology and MicrobiologySarcoidosis is a multisystemic granulomatous disorder of unknown cause, characterized by formation of immune granulomas in various organs, mainly in lungs. Currently, two main phenotypes of pulmonary sarcoidosis are described, i.e., Lofgren’s syndrome (LS) is an acute form with favorable outcome, and non-Lofgren’s syndrome (nLS) is a chronic type of disease with a high risk of pulmonary fibrosis. Our study was aimed to investigate the balance of main “polarized” CD4+ central and effector memory T cells from treatment-naive patients with pulmonary sarcoidosis (LS (n = 19) and nLS (n = 63)) compared to healthy volunteers (HC, n = 48). This marker might be used as immunological markers for predicting severity of this disorder. Multicolor flow cytometry analysis demonstrated that the patients with nLS showed significantly low levels of relative and absolute numbers of CD3+CD4+ lymphocytes if compared to patients with LS and control group (38.94% (31.33-44.24) versus 48.96% (43.34-53.54) and 47.63% (43.82-52.73), p < 0.001 in both cases). Moreover, patients with nLS had reduced frequencies and absolute numbers of “naive”, CM and EM Th cells if compared with healthy controls. Furthermore, the patients with LS showed increased relative and absolute numbers of peripheral blood EM Th cells, capable for migration to peripheral inflamed tissues, when compared with nLS. Finally, patients with LS had increased frequencies and absolute numbers of effector TEMRA Th cells as compared to HC and nLS. Next, significant differences Th1 and Th2 cells frequencies were shown between the patients with nLS and HC (9.64% (7.06-13.65) versus 13.80% (11.24-18.03) with p < 0.001, and 11.96% (9.86-14.78) versus 10.67% (9.13-12.98) with p = 0.048, respectively). But there were no significant differences in the relative numbers of CXCR5-CCR6+Th17 and CXCR5+ follicular T helper cells (Tfh) between the groups. Finally, both groups of patients with pulmonary sarcoidosis contained low proportions of “non-classical” Th17 and DN Th17 cell, but increased levels of DP Th17 cells within total CXCR5-CCR6+ CM Th if compared with HC. Nevertheless, patients with nLS had increased frequency of “classical” Th17 in comparison with healthy controls. A very similar imbalance between different Th17 cell subsets was observed within total CXCR5CCR6+ effector memory Th, that were able to migrate from the bloodstream to the sites of infection, or tissue injury. Taken together, the data suggest that the proportions of Th17 cell subsets in pulmonary sarcoidosis can be evaluated as a diagnostic and/or prognostic marker in clinical practice and these cells could serve as a new therapeutic target.https://www.mimmun.ru/mimmun/article/view/2468sarcoidosiscd4+t cellsth cell differentiationth17 cell subsetsth17.1flow cytometry
spellingShingle I. V. Kudryavtsev
N. M. Lazareva
O. P. Baranova
M. K. Serebriakova
T. P. Ses’
M. M. Ilkovich
A. A. Totolian
Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients
Медицинская иммунология
sarcoidosis
cd4+t cells
th cell differentiation
th17 cell subsets
th17.1
flow cytometry
title Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients
title_full Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients
title_fullStr Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients
title_full_unstemmed Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients
title_short Peripheral blood T helper cell subsets in Löfgren’s and non-Löfgren’s syndrome patients
title_sort peripheral blood t helper cell subsets in lofgren s and non lofgren s syndrome patients
topic sarcoidosis
cd4+t cells
th cell differentiation
th17 cell subsets
th17.1
flow cytometry
url https://www.mimmun.ru/mimmun/article/view/2468
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