RGD Reference Report - T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease. - Rat Genome Database

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

Authors: Boin, F  De Fanis, U  Bartlett, SJ  Wigley, FM  Rosen, A  Casolaro, V 
Citation: Boin F, etal., Arthritis Rheum. 2008 Apr;58(4):1165-74.
RGD ID: 4892085
Pubmed: PMID:18383361   (View Abstract at PubMed)
PMCID: PMC2662772   (View Article at PubMed Central)
DOI: DOI:10.1002/art.23406   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
interstitial lung disease  IEP 4892085associated with Scleroderma more ...RGD 
interstitial lung disease  ISOCCR5 (Homo sapiens)4892085; 4892085associated with Scleroderma more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Mus musculus)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Homo sapiens)
CCR5  (C-C motif chemokine receptor 5)


Additional Information