Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome

Introduction: The role of the immune response in the pathogenesis of antiphospholipid syndrome (APS) remains elusive. It is possible that differences in the frequencies of Th17 cells and/or defects in the immunoregulatory mechanisms are involved in the pathogenesis of APS. Our aim was to determine t...

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Main Authors: Lorena Álvarez-Rodríguez, Víctor Martínez-Taboada, Jaime Calvo-Alén, Iñaki Beares, Ignacio Villa, Marcos López-Hoyos
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.00391/full
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author Lorena Álvarez-Rodríguez
Víctor Martínez-Taboada
Jaime Calvo-Alén
Iñaki Beares
Ignacio Villa
Marcos López-Hoyos
author_facet Lorena Álvarez-Rodríguez
Víctor Martínez-Taboada
Jaime Calvo-Alén
Iñaki Beares
Ignacio Villa
Marcos López-Hoyos
author_sort Lorena Álvarez-Rodríguez
collection DOAJ
description Introduction: The role of the immune response in the pathogenesis of antiphospholipid syndrome (APS) remains elusive. It is possible that differences in the frequencies of Th17 cells and/or defects in the immunoregulatory mechanisms are involved in the pathogenesis of APS. Our aim was to determine the peripheral blood Th cells phenotype and the circulating cytokine profile in patients with primary APS (pAPS) and compare it with systemic lupus erythemathosus (SLE) as disease control group.Methods: The frequencies of circulating regulatory T cells (Tregs) were determined in PBMCs from 36 patients with pAPS by flow cytometry. As control groups we included 21 age- and gender-matched healthy controls (HC) and 11 patients with SLE. The suppressive capacity of Tregs was evaluated in vitro by coculture assay. On the other hand, intracellular cytokine production was assessed in Th1, Th2, and Th17 cells and circulating IL-6, IL-10, and IL-35 were measured by Cytometric Bead Array and ELISA. The quantification of Th master gene expression levels was performed by real time quantitative PCR.Results: pAPS patients and SLE patients did not show differences in the percentage or number of Tregs compared to HC. The suppressive capacity of Tregs was also similar in the three study group. Instead, we found higher FoxP3·mRNA expression levels in pAPS patients and HC than SLE patients. Regarding the Th17 response, patients with pAPS and HC showed a significantly lower frequency of circulating Th17 cells than SLE. However, no differences were observed in the Th1 response between patients and controls. Thus, increased Th17/Th1 and Th17/Treg ratios were found in SLE patients but not in pAPS patients. pAPS and SLE patients had higher serum IL-6 levels than HC but there was not difference between both disease groups. Besides, a significant increase in the immunosuppressive cytokine levels was observed only in pAPS as compared to HC.Conclusions: Our data demonstrate an increased inflammatory profile of peripheral blood CD4+ T cells from SLE as compared with pAPS mostly due to an increased Th17 response. In conclusion, there seems not to be a direct pathogenic role for Th cells in pAPS but in SLE.
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spelling doaj.art-81af923b17634bd5be6fc199c6f1dcad2022-12-21T19:11:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00391433210Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid SyndromeLorena Álvarez-Rodríguez0Víctor Martínez-Taboada1Jaime Calvo-Alén2Iñaki Beares3Ignacio Villa4Marcos López-Hoyos5Transplantation and Autoimmunity Laboratory, Rheumatology Department, University Hospital Marqués de Valdecilla-IDIVAL, Santander, SpainFaculty of Medicine, Rheumatology Department, University Hospital Marqués de Valdecilla-IDIVAL, Cantabria University, Santander, SpainRheumatology Department, University Hospital Araba, Vitoria-Gasteiz, SpainTransplantation and Autoimmunity Laboratory, Rheumatology Department, University Hospital Marqués de Valdecilla-IDIVAL, Santander, SpainRheumatology Department, Hospital Sierrallana, Torrelavega, SpainImmunology Department, University Hospital Marqués de Valdecilla-IDIVAL, Cantabria University, Santander, SpainIntroduction: The role of the immune response in the pathogenesis of antiphospholipid syndrome (APS) remains elusive. It is possible that differences in the frequencies of Th17 cells and/or defects in the immunoregulatory mechanisms are involved in the pathogenesis of APS. Our aim was to determine the peripheral blood Th cells phenotype and the circulating cytokine profile in patients with primary APS (pAPS) and compare it with systemic lupus erythemathosus (SLE) as disease control group.Methods: The frequencies of circulating regulatory T cells (Tregs) were determined in PBMCs from 36 patients with pAPS by flow cytometry. As control groups we included 21 age- and gender-matched healthy controls (HC) and 11 patients with SLE. The suppressive capacity of Tregs was evaluated in vitro by coculture assay. On the other hand, intracellular cytokine production was assessed in Th1, Th2, and Th17 cells and circulating IL-6, IL-10, and IL-35 were measured by Cytometric Bead Array and ELISA. The quantification of Th master gene expression levels was performed by real time quantitative PCR.Results: pAPS patients and SLE patients did not show differences in the percentage or number of Tregs compared to HC. The suppressive capacity of Tregs was also similar in the three study group. Instead, we found higher FoxP3·mRNA expression levels in pAPS patients and HC than SLE patients. Regarding the Th17 response, patients with pAPS and HC showed a significantly lower frequency of circulating Th17 cells than SLE. However, no differences were observed in the Th1 response between patients and controls. Thus, increased Th17/Th1 and Th17/Treg ratios were found in SLE patients but not in pAPS patients. pAPS and SLE patients had higher serum IL-6 levels than HC but there was not difference between both disease groups. Besides, a significant increase in the immunosuppressive cytokine levels was observed only in pAPS as compared to HC.Conclusions: Our data demonstrate an increased inflammatory profile of peripheral blood CD4+ T cells from SLE as compared with pAPS mostly due to an increased Th17 response. In conclusion, there seems not to be a direct pathogenic role for Th cells in pAPS but in SLE.https://www.frontiersin.org/article/10.3389/fimmu.2019.00391/fullpAPSSLETh1Th17Treginflammation
spellingShingle Lorena Álvarez-Rodríguez
Víctor Martínez-Taboada
Jaime Calvo-Alén
Iñaki Beares
Ignacio Villa
Marcos López-Hoyos
Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome
Frontiers in Immunology
pAPS
SLE
Th1
Th17
Treg
inflammation
title Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome
title_full Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome
title_fullStr Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome
title_full_unstemmed Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome
title_short Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome
title_sort altered th17 treg ratio in peripheral blood of systemic lupus erythematosus but not primary antiphospholipid syndrome
topic pAPS
SLE
Th1
Th17
Treg
inflammation
url https://www.frontiersin.org/article/10.3389/fimmu.2019.00391/full
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