T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease

Francesco Boin, Umberto De Fanis, Susan J. Bartlett, Fredrick Wigley, Antony Rosen, Vincenzo Casolaro

Research output: Contribution to journalArticle

Abstract

Objective. Lung involvement is the leading cause of morbidity and mortality in systemic sclerosis (SSc; scleroderma), and interstitial lung disease (ILD) is the most common pulmonary manifestation. An abnormal profibrotic Th2/Tc2-polarized T cell response is postulated to mediate tissue damage and fibrosis. The aim of this study was to investigate whether a polarized T cell phenotype in SSc is associated with lung disease or other clinical manifestations of SSc. Methods. Circulating T cells were characterized by flow cytometry in 62 patients with SSc and 36 healthy control subjects, using antibodies against CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1-specific), and prostaglandin D2 receptor CRTH2 (Th2/Tc2-specific). The ratio between CCR5 and CRTH2 T cell frequencies was used to quantify type 1 (high-ratio) or type 2 (low-ratio) immune polarization. Results. Patients with SSc exhibited lower CCR5/ CRTH2 T cell ratios than those exhibited by control subjects (P <0.0001), indicating a Th2/Tc2-polarized phenotype. Markedly reduced CCR5/CRTH2 T cell ratios were observed in SSc patients with ILD compared with SSc patients without ILD (P <0.0001), particularly in patients with active ILD (P <0.0001) compared with those with stable lung function. Lower CCR5/ CRTH2 ratios were strongly associated with a lower value for the percent predicted forced vital capacity (P <0.0001). In patients with an estimated right ventricular systolic pressure >35 mm Hg, suggestive of pulmonary vascular disease, a lower value for the percent predicted diffusing capacity (DLco) was associated with higher CCR5/CRTH2 T cell ratios (Th1/Tc1) (P = 0.009), while in those with right ventricular systolic pressure

Original languageEnglish (US)
Pages (from-to)1165-1174
Number of pages10
JournalArthritis and Rheumatism
Volume58
Issue number4
DOIs
StatePublished - Apr 2008

Fingerprint

Lung Diseases
T-Lymphocytes
Phenotype
Lung
Systemic Scleroderma
Chemokine Receptors
Interstitial Lung Diseases
Ventricular Pressure
Vascular Diseases
Healthy Volunteers
Flow Cytometry
Fibrosis
Blood Pressure
Morbidity
Mortality
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease. / Boin, Francesco; De Fanis, Umberto; Bartlett, Susan J.; Wigley, Fredrick; Rosen, Antony; Casolaro, Vincenzo.

In: Arthritis and Rheumatism, Vol. 58, No. 4, 04.2008, p. 1165-1174.

Research output: Contribution to journalArticle

Boin, Francesco ; De Fanis, Umberto ; Bartlett, Susan J. ; Wigley, Fredrick ; Rosen, Antony ; Casolaro, Vincenzo. / T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease. In: Arthritis and Rheumatism. 2008 ; Vol. 58, No. 4. pp. 1165-1174.
@article{99f630fb150d46199a53c0cb310e673d,
title = "T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease",
abstract = "Objective. Lung involvement is the leading cause of morbidity and mortality in systemic sclerosis (SSc; scleroderma), and interstitial lung disease (ILD) is the most common pulmonary manifestation. An abnormal profibrotic Th2/Tc2-polarized T cell response is postulated to mediate tissue damage and fibrosis. The aim of this study was to investigate whether a polarized T cell phenotype in SSc is associated with lung disease or other clinical manifestations of SSc. Methods. Circulating T cells were characterized by flow cytometry in 62 patients with SSc and 36 healthy control subjects, using antibodies against CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1-specific), and prostaglandin D2 receptor CRTH2 (Th2/Tc2-specific). The ratio between CCR5 and CRTH2 T cell frequencies was used to quantify type 1 (high-ratio) or type 2 (low-ratio) immune polarization. Results. Patients with SSc exhibited lower CCR5/ CRTH2 T cell ratios than those exhibited by control subjects (P <0.0001), indicating a Th2/Tc2-polarized phenotype. Markedly reduced CCR5/CRTH2 T cell ratios were observed in SSc patients with ILD compared with SSc patients without ILD (P <0.0001), particularly in patients with active ILD (P <0.0001) compared with those with stable lung function. Lower CCR5/ CRTH2 ratios were strongly associated with a lower value for the percent predicted forced vital capacity (P <0.0001). In patients with an estimated right ventricular systolic pressure >35 mm Hg, suggestive of pulmonary vascular disease, a lower value for the percent predicted diffusing capacity (DLco) was associated with higher CCR5/CRTH2 T cell ratios (Th1/Tc1) (P = 0.009), while in those with right ventricular systolic pressure",
author = "Francesco Boin and {De Fanis}, Umberto and Bartlett, {Susan J.} and Fredrick Wigley and Antony Rosen and Vincenzo Casolaro",
year = "2008",
month = "4",
doi = "10.1002/art.23406",
language = "English (US)",
volume = "58",
pages = "1165--1174",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease

AU - Boin, Francesco

AU - De Fanis, Umberto

AU - Bartlett, Susan J.

AU - Wigley, Fredrick

AU - Rosen, Antony

AU - Casolaro, Vincenzo

PY - 2008/4

Y1 - 2008/4

N2 - Objective. Lung involvement is the leading cause of morbidity and mortality in systemic sclerosis (SSc; scleroderma), and interstitial lung disease (ILD) is the most common pulmonary manifestation. An abnormal profibrotic Th2/Tc2-polarized T cell response is postulated to mediate tissue damage and fibrosis. The aim of this study was to investigate whether a polarized T cell phenotype in SSc is associated with lung disease or other clinical manifestations of SSc. Methods. Circulating T cells were characterized by flow cytometry in 62 patients with SSc and 36 healthy control subjects, using antibodies against CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1-specific), and prostaglandin D2 receptor CRTH2 (Th2/Tc2-specific). The ratio between CCR5 and CRTH2 T cell frequencies was used to quantify type 1 (high-ratio) or type 2 (low-ratio) immune polarization. Results. Patients with SSc exhibited lower CCR5/ CRTH2 T cell ratios than those exhibited by control subjects (P <0.0001), indicating a Th2/Tc2-polarized phenotype. Markedly reduced CCR5/CRTH2 T cell ratios were observed in SSc patients with ILD compared with SSc patients without ILD (P <0.0001), particularly in patients with active ILD (P <0.0001) compared with those with stable lung function. Lower CCR5/ CRTH2 ratios were strongly associated with a lower value for the percent predicted forced vital capacity (P <0.0001). In patients with an estimated right ventricular systolic pressure >35 mm Hg, suggestive of pulmonary vascular disease, a lower value for the percent predicted diffusing capacity (DLco) was associated with higher CCR5/CRTH2 T cell ratios (Th1/Tc1) (P = 0.009), while in those with right ventricular systolic pressure

AB - Objective. Lung involvement is the leading cause of morbidity and mortality in systemic sclerosis (SSc; scleroderma), and interstitial lung disease (ILD) is the most common pulmonary manifestation. An abnormal profibrotic Th2/Tc2-polarized T cell response is postulated to mediate tissue damage and fibrosis. The aim of this study was to investigate whether a polarized T cell phenotype in SSc is associated with lung disease or other clinical manifestations of SSc. Methods. Circulating T cells were characterized by flow cytometry in 62 patients with SSc and 36 healthy control subjects, using antibodies against CD3, CD4, CD8, chemokine receptor CCR5 (Th1/Tc1-specific), and prostaglandin D2 receptor CRTH2 (Th2/Tc2-specific). The ratio between CCR5 and CRTH2 T cell frequencies was used to quantify type 1 (high-ratio) or type 2 (low-ratio) immune polarization. Results. Patients with SSc exhibited lower CCR5/ CRTH2 T cell ratios than those exhibited by control subjects (P <0.0001), indicating a Th2/Tc2-polarized phenotype. Markedly reduced CCR5/CRTH2 T cell ratios were observed in SSc patients with ILD compared with SSc patients without ILD (P <0.0001), particularly in patients with active ILD (P <0.0001) compared with those with stable lung function. Lower CCR5/ CRTH2 ratios were strongly associated with a lower value for the percent predicted forced vital capacity (P <0.0001). In patients with an estimated right ventricular systolic pressure >35 mm Hg, suggestive of pulmonary vascular disease, a lower value for the percent predicted diffusing capacity (DLco) was associated with higher CCR5/CRTH2 T cell ratios (Th1/Tc1) (P = 0.009), while in those with right ventricular systolic pressure

UR - http://www.scopus.com/inward/record.url?scp=42449114776&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42449114776&partnerID=8YFLogxK

U2 - 10.1002/art.23406

DO - 10.1002/art.23406

M3 - Article

C2 - 18383361

AN - SCOPUS:42449114776

VL - 58

SP - 1165

EP - 1174

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 4

ER -