T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease.
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.


CONCLUSIONS
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.
Boin
Francesco
F
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. fboin1@jhmi.edu
De Fanis
Umberto
U
Bartlett
Susan J
SJ
Wigley
Fredrick M
FM
Rosen
Antony
A
Casolaro
Vincenzo
V
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012595:Scleroderma, Systemic / Q000145:classification* / Q000150:complications / Q000276:immunology*; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic; D018417:Th1 Cells; D018418:Th2 Cells
D015415:Biomarkers