Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders

Peter Szodoray, Britt Nakken, S. Baráth, I. Csípő, G. Nagy, Fadi El-Hage, Liv T. Osnes, G. Szegedi, E. Bodolay

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Abstract

A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4+CD25brightFoxP3+; nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker.

Original languageEnglish
Pages (from-to)1510-1518
Number of pages9
JournalHuman Immunology
Volume74
Issue number12
DOIs
Publication statusPublished - 2013

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Th17 Cells
Connective Tissue Diseases
Regulatory T-Lymphocytes
Autoimmune Diseases
Interleukin-10
Disease Progression
T-Lymphocytes
Interleukin-17
Flow Cytometry
Population

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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title = "Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders",
abstract = "A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4+CD25brightFoxP3+; nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3{\%} of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker.",
author = "Peter Szodoray and Britt Nakken and S. Bar{\'a}th and I. Cs{\'i}pő and G. Nagy and Fadi El-Hage and Osnes, {Liv T.} and G. Szegedi and E. Bodolay",
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T1 - Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders

AU - Szodoray, Peter

AU - Nakken, Britt

AU - Baráth, S.

AU - Csípő, I.

AU - Nagy, G.

AU - El-Hage, Fadi

AU - Osnes, Liv T.

AU - Szegedi, G.

AU - Bodolay, E.

PY - 2013

Y1 - 2013

N2 - A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4+CD25brightFoxP3+; nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker.

AB - A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4+CD25brightFoxP3+; nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker.

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