T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease

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

Research output: Contribution to journalArticlepeer-review

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 <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.

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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