![[Visit Client Website]](images/banner.gif)
Presentation Number: 1154
Purpose: The immune response in Systemic Sclerosis (SSc) displays a selective type 2 (Th2/Tc2) T cell cytokine profile and it is suggested participating in the pathogenesis of tissue fibrosis. We investigated whether the presence of this skewed phenotype is associated with distinct clinical manifestations and correlates with disease outcome in a well defined cohort of SSc patients.
Methods: Peripheral blood was collected from 53 consecutive patients meeting ACR criteria for SSc (21 limited and 32 diffuse) and from 32 healthy controls. Patients were further categorized as having interstitial lung disease (ILD) based on FVC < 80% (predicted) and a normal echocardiographic estimated right ventricular systolic pressure (eRVSP <30 mmHg). T cell subsets were characterized by flow cytometry using antibodies against CD3, CD4, CD8, the chemokine receptor CCR5 (Th1/Tc1 specific) and the PGD2 receptor CRTH2 (Th2/Tc2 specific). The ratio of CCR5/CRTH2-positive cells was used to determine polarization of the immune response towards a type 1 (high) or type 2 (low) phenotype. T cells ratios in controls and patients were compared using a Mann-Whitney non-parametric test. Clinical correlation coefficients were calculated using Spearman’s rank test.
Results: SSc patients presented a CCR5/CRTH2 ratio significantly lower than controls in CD3+ (p<0.0001), CD4+ (p=0.001) and CD8+ (p<0.0001) T cells confirming a Th2/Tc2 skewed immunophenotype in this disease. No difference was noted in limited vs. diffuse SSc subjects. In contrast, CCR5/CRTH2 ratios were significantly lower in patients with ILD vs. those without (CD3+ p=0.001). A decreased FVC (% predicted) was strongly correlated with a lower CCR5/CRTH2 ratio (r=0.490; p=0.001). Changes in the DLCO (% predicted) and CCR5/CRTH2 ratio did not show a significant correlation (r=0.301; p=0.06). However, when the patients were further stratified by their eRVSP, in those with normal eRVSP (<30 mmHg) a lower DLCO% was correlated with a lower CCR5/CRTH2 ratio (r=0.751, p=0.0001), while in those with elevated eRVSP (>30 mmHg) a lower DLCO% was correlated with a higher CCR5/CRTH2 ratio (r=-0.596, p=0.01) (Figure).
Conclusions: The strong association between the predominance of a Th2/Tc2 T cell immunophenotype with ILD and a Th1/Tc1 with clinical evidence of pulmonary hypertension suggests that in SSc patients the polarization of the immune response may be implicated in the pathogenesis of specific disease manifestations. Prospective measuring of CCR5/CRTH2 ratios may prove to be a novel and useful tool to predict distinct clinical outcomes and maybe to measure disease activity.
Methods: Peripheral blood was collected from 53 consecutive patients meeting ACR criteria for SSc (21 limited and 32 diffuse) and from 32 healthy controls. Patients were further categorized as having interstitial lung disease (ILD) based on FVC < 80% (predicted) and a normal echocardiographic estimated right ventricular systolic pressure (eRVSP <30 mmHg). T cell subsets were characterized by flow cytometry using antibodies against CD3, CD4, CD8, the chemokine receptor CCR5 (Th1/Tc1 specific) and the PGD2 receptor CRTH2 (Th2/Tc2 specific). The ratio of CCR5/CRTH2-positive cells was used to determine polarization of the immune response towards a type 1 (high) or type 2 (low) phenotype. T cells ratios in controls and patients were compared using a Mann-Whitney non-parametric test. Clinical correlation coefficients were calculated using Spearman’s rank test.
Results: SSc patients presented a CCR5/CRTH2 ratio significantly lower than controls in CD3+ (p<0.0001), CD4+ (p=0.001) and CD8+ (p<0.0001) T cells confirming a Th2/Tc2 skewed immunophenotype in this disease. No difference was noted in limited vs. diffuse SSc subjects. In contrast, CCR5/CRTH2 ratios were significantly lower in patients with ILD vs. those without (CD3+ p=0.001). A decreased FVC (% predicted) was strongly correlated with a lower CCR5/CRTH2 ratio (r=0.490; p=0.001). Changes in the DLCO (% predicted) and CCR5/CRTH2 ratio did not show a significant correlation (r=0.301; p=0.06). However, when the patients were further stratified by their eRVSP, in those with normal eRVSP (<30 mmHg) a lower DLCO% was correlated with a lower CCR5/CRTH2 ratio (r=0.751, p=0.0001), while in those with elevated eRVSP (>30 mmHg) a lower DLCO% was correlated with a higher CCR5/CRTH2 ratio (r=-0.596, p=0.01) (Figure).
Conclusions: The strong association between the predominance of a Th2/Tc2 T cell immunophenotype with ILD and a Th1/Tc1 with clinical evidence of pulmonary hypertension suggests that in SSc patients the polarization of the immune response may be implicated in the pathogenesis of specific disease manifestations. Prospective measuring of CCR5/CRTH2 ratios may prove to be a novel and useful tool to predict distinct clinical outcomes and maybe to measure disease activity.
F. Boin, None.