Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile
Immune cell hyperactivation along with cytokines they overproduce plays an important role in sarcoidosis and related disease pathogenesis. A central place in the immunopathogenesis of sarcoidosis is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 sub...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | Russian |
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St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists
2023-06-01
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| Series: | Медицинская иммунология |
| Subjects: | |
| Online Access: | https://www.mimmun.ru/mimmun/article/view/2694 |
| _version_ | 1824243029556330496 |
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| author | N. M. Lazareva I. V. Kudryavtsev O. P. Baranova D. V. Isakov M. K. Serebriakova A. A. Bazhanov N. A. Arsentieva N. E. Liubimova T. P. Ses’ M. M. Ilkovich A. A. Totolian |
| author_facet | N. M. Lazareva I. V. Kudryavtsev O. P. Baranova D. V. Isakov M. K. Serebriakova A. A. Bazhanov N. A. Arsentieva N. E. Liubimova T. P. Ses’ M. M. Ilkovich A. A. Totolian |
| author_sort | N. M. Lazareva |
| collection | DOAJ |
| description | Immune cell hyperactivation along with cytokines they overproduce plays an important role in sarcoidosis and related disease pathogenesis. A central place in the immunopathogenesis of sarcoidosis is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 subsets and relevant signature cytokines. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 123): 18% with acute and 82% with chronic course. The control group — samples from healthy volunteers (n = 43). T cell subset composition was assessed by flow cytometry. Cytokine concentrations (pg/mL) were measured by multiplex analysis using xMAP technology (Luminex). The level of “classical” Th17 turned out to be significantly reduced in acute vs chronic sarcoidosis: 28.3% vs 33.3% (p = 0.046). The level of “double-positive” Th17 (DP Th17) was significantly increased in chronic and acute vs control group: 31.7% and 34.2% vs 26.2% (p < 0.001 in both cases), without differences patient inter-group; “non-classical” Th17.1 were shown to have significantly reduced level only in chronic vs healthy subjects: 27.9% and 35.9% (p < 0.001). Clinical and laboratory diagnostic characteristics for blood DP Th17 levels in CD45RA-negative Th effector memory cells in sarcoidosis: in acute sarcoidosis vs healthy subjects, they were characterized by sensitivity — 82%; specificity — 71%, whereas in chronic: 67% and 56%, respectively. In patients with sarcoidosis vs healthy subjects were found to have significantly increased level of IL-12 (p70) — 1.3 vs 0.56, p = 0.028; IL-17A — 1.5 vs 0.43, p < 0.001; IFNγ — 4.1 vs 1.1, p < 0.001; TNFα — 21.7 vs 6.7, p < 0.001. Thus, CCR6+ Th17 and DP Th17 subsets and relevant signature cytokines are important in diagnostics of sarcoidosis of varying clinical course: a direct correlation was shown between the level of angiotensin-converting enzyme activity and percentage of memory DP Th17; disease progression vs regression had significantly reduced absolute number of total CD45RA- memory and CM Th17; extrapulmonary manifestations had a significantly increased percentage of DP Th17 CD45RA- and EM DP Th17; in chronic sarcoidosis are significantly increased concentration of IL-17A, IFNγ, IL-12 and positively correlation between IFNγ and the activity of angiotensin-converting enzyme. |
| first_indexed | 2024-03-08T05:46:26Z |
| format | Article |
| id | doaj.art-262bf29d573e44e2aef43c438dac5fa2 |
| institution | Directory Open Access Journal |
| issn | 1563-0625 2313-741X |
| language | Russian |
| last_indexed | 2025-02-16T19:22:04Z |
| publishDate | 2023-06-01 |
| publisher | St. Petersburg branch of the Russian Association of Allergologists and Clinical Immunologists |
| record_format | Article |
| series | Медицинская иммунология |
| spelling | doaj.art-262bf29d573e44e2aef43c438dac5fa22025-01-23T13:44:06ZrusSt. Petersburg branch of the Russian Association of Allergologists and Clinical ImmunologistsМедицинская иммунология1563-06252313-741X2023-06-012551049105810.15789/1563-0625-SCP-26941759Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profileN. M. Lazareva0I. V. Kudryavtsev1O. P. Baranova2D. V. Isakov3M. K. Serebriakova4A. A. Bazhanov5N. A. Arsentieva6N. E. Liubimova7T. P. Ses’8M. M. Ilkovich9A. A. Totolian10First St. Petersburg State I. Pavlov Medical University; Russian Research Institute of Hematology and Transfusiology of the Federal Medical and Biological AgencyFirst 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 UniversitySaint Petersburg Pasteur InstituteSaint Petersburg Pasteur InstituteFirst St. Petersburg State I. Pavlov Medical UniversityFirst St. Petersburg State I. Pavlov Medical UniversityFirst St. Petersburg State I. Pavlov Medical University; Saint Petersburg Pasteur InstituteImmune cell hyperactivation along with cytokines they overproduce plays an important role in sarcoidosis and related disease pathogenesis. A central place in the immunopathogenesis of sarcoidosis is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 subsets and relevant signature cytokines. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 123): 18% with acute and 82% with chronic course. The control group — samples from healthy volunteers (n = 43). T cell subset composition was assessed by flow cytometry. Cytokine concentrations (pg/mL) were measured by multiplex analysis using xMAP technology (Luminex). The level of “classical” Th17 turned out to be significantly reduced in acute vs chronic sarcoidosis: 28.3% vs 33.3% (p = 0.046). The level of “double-positive” Th17 (DP Th17) was significantly increased in chronic and acute vs control group: 31.7% and 34.2% vs 26.2% (p < 0.001 in both cases), without differences patient inter-group; “non-classical” Th17.1 were shown to have significantly reduced level only in chronic vs healthy subjects: 27.9% and 35.9% (p < 0.001). Clinical and laboratory diagnostic characteristics for blood DP Th17 levels in CD45RA-negative Th effector memory cells in sarcoidosis: in acute sarcoidosis vs healthy subjects, they were characterized by sensitivity — 82%; specificity — 71%, whereas in chronic: 67% and 56%, respectively. In patients with sarcoidosis vs healthy subjects were found to have significantly increased level of IL-12 (p70) — 1.3 vs 0.56, p = 0.028; IL-17A — 1.5 vs 0.43, p < 0.001; IFNγ — 4.1 vs 1.1, p < 0.001; TNFα — 21.7 vs 6.7, p < 0.001. Thus, CCR6+ Th17 and DP Th17 subsets and relevant signature cytokines are important in diagnostics of sarcoidosis of varying clinical course: a direct correlation was shown between the level of angiotensin-converting enzyme activity and percentage of memory DP Th17; disease progression vs regression had significantly reduced absolute number of total CD45RA- memory and CM Th17; extrapulmonary manifestations had a significantly increased percentage of DP Th17 CD45RA- and EM DP Th17; in chronic sarcoidosis are significantly increased concentration of IL-17A, IFNγ, IL-12 and positively correlation between IFNγ and the activity of angiotensin-converting enzyme.https://www.mimmun.ru/mimmun/article/view/2694sarcoidosiscd4<sup>+</sup> t cellsth cell differentiationth17 cell subsetsflow cytometrycytokines |
| spellingShingle | N. M. Lazareva I. V. Kudryavtsev O. P. Baranova D. V. Isakov M. K. Serebriakova A. A. Bazhanov N. A. Arsentieva N. E. Liubimova T. P. Ses’ M. M. Ilkovich A. A. Totolian Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile Медицинская иммунология sarcoidosis cd4<sup>+</sup> t cells th cell differentiation th17 cell subsets flow cytometry cytokines |
| title | Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile |
| title_full | Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile |
| title_fullStr | Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile |
| title_full_unstemmed | Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile |
| title_short | Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile |
| title_sort | sarcoidosis clinical picture governs alterations in type 17 t helper cell subset composition and cytokine profile |
| topic | sarcoidosis cd4<sup>+</sup> t cells th cell differentiation th17 cell subsets flow cytometry cytokines |
| url | https://www.mimmun.ru/mimmun/article/view/2694 |
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