Abstract
Systemic sclerosis (SSc) is a multisystem fibrotic disorder with autoimmune background. Accumulating evidence has highlighted the importance of T helper (Th) 2 cells in the pathogenesis of SSc and its complications. Because thymus and activation-regulated chemokine (TARC) is a potent chemoattractant for Th2 cells, we measured serum TARC levels in SSc patients and analyzed their correlation with interstitial lung disease (ILD), a major complication of SSc. Serum TARC levels were significantly elevated in patients with SSc, especially in those with the diffuse subtype, compared with healthy controls. In particular, dcSSc patients with SSc-associated ILD (SSc-ILD) showed higher TARC levels than those without SSc-ILD. However, there was no significant correlation between serum TARC levels and pulmonary function in SSc patients. Serum TARC levels did not correlate with serum levels of interleukin-13, an important Th2 cytokine, either. Furthermore, in the longitudinal study, serum TARC levels did not predict the onset or progression of SSc-ILD in patients with SSc. These results were in contrast with those of KL-6 and surfactant protein D, which correlated well with the onset, severity, and progression of SSc-ILD. Overall, these results suggest that serum TARC levels are not suitable for monitoring the disease activity of SSc-ILD.
Highlights
Systemic sclerosis (SSc) is a progressive connective tissue disease in which excessive fibrosis of the skin and internal organs leads to diverse clinical manifestations that are highly distressing and often life-threatening [1,2]
0.0001 for SP-D) and %DLco (r = −0.438, p < 0.0001 for KL-6, r = −0.456, p < 0.0001 for SPSP-D). These results suggest that serum thymus and activation-regulated chemokine (TARC) levels are not associated with the severity of
Serum KL-6 levels were significantly higher in SSc patients who developed SSc-interstitial lung disease (ILD) during the followup period compared with those who did not (480.0 ± 149.5 pg/mL vs. 264.7 ± 98.04 pg/mL, 7 of 13 was Similar trends were obtained with serum SP-D levels, but the difference not statistically significant (150.5 ± 117.6 pg/mL vs. 55.06 ± 30.06, p = 0.078). These results suggest that serum TARC levels cannot be used to predict the onset of SSc-associated ILD (SSc-ILD)
Summary
Systemic sclerosis (SSc) is a progressive connective tissue disease in which excessive fibrosis of the skin and internal organs leads to diverse clinical manifestations that are highly distressing and often life-threatening [1,2]. Abnormalities of T cells have been extensively studied in both patients and animal models of SSc [5,6]. T-cell immune responses in SSc are heavily skewed toward T helper (Th) 2 with increased production of Th2 cytokines such as interleukin IL-4 and IL-13 [7,8,9]. Th2 cells drive the pathological cascade of SSc through multiple mechanisms [10]. Various cytokines and chemokines that are involved in activation, migration, and differentiation of Th2 cells have been implicated in the development of SSc [11,12,13,14,15]
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