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 M.
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 <35 mm Hg, a lower value for the percent predicted DLco correlated with lower ratios (Th2/Tc2) (P < 0.0001), as observed for ILD. Conclusion. T cell polarization in SSc is strongly associated with specific manifestations of lung disease. Measurement of T cell polarization may represent a valuable tool to monitor disease activity and predict clinical outcomes in SSc patients with lung disease.
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 <35 mm Hg, a lower value for the percent predicted DLco correlated with lower ratios (Th2/Tc2) (P < 0.0001), as observed for ILD. Conclusion. T cell polarization in SSc is strongly associated with specific manifestations of lung disease. Measurement of T cell polarization may represent a valuable tool to monitor disease activity and predict clinical outcomes in SSc patients with lung disease.
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U2 - 10.1002/art.23406
DO - 10.1002/art.23406
M3 - Article
C2 - 18383361
AN - SCOPUS:42449114776
SN - 0004-3591
VL - 58
SP - 1165
EP - 1174
JO - Arthritis and rheumatism
JF - Arthritis and rheumatism
IS - 4
ER -