Elevated serum CC chemokine ligand (CCL)18 reflects lung fibrosis activity in systemic sclerosis (SSc) and could be an early marker of lung function worsening. Therefore, we sought to evaluate whether serum CCL18 levels at baseline could predict worsening of lung disease in SSc.In this prospective study, 83 SSc patients were analysed longitudinally over a 4-yr observation period for the risk of occurrence of combined deleterious events, defined as a 10% decrease from baseline of total lung capacity or forced vital capacity % predicted, or death, according to serum CCL18 at inclusion. Receiver operating characteristic (ROC) curve analysis was performed for prediction of events during the first year after inclusion.The best cut-off level of serum CCL18 for prediction of a combined event within the follow-up period was 187 ng·mL⁻¹, with 53% sensitivity and 96% specificity (area under the ROC curve 0.86; p<0.001). After a mean±sdfollow-up of 33.7±10.8 months, a higher rate of disease progression occurred in the group with serum CCL18 levels >187 ng·mL⁻¹. The adjusted hazard ratio was 5.36 (95% CI 2.44–11.75; p<0.001).In summary, serum CCL18 is an accurate predictive biomarker for the identification of patients with a higher risk of subsequent scleroderma lung disease worsening.

The reported deep learning–based method can be used to evaluate the extent of interstitial lung disease in systemic sclerosis with results comparable to those of radiologists. Purpose To develop a deep learning algorithm for the automatic assessment of the extent of systemic sclerosis (SSc)–related interstitial lung disease (ILD) on chest CT images. Materials and Methods...

Background: Systemic sclerosis (SSc) is a connective-tissue disease characterized by vascular injury, immune-system disorders, and excessive fibrosis of the skin and multiple internal organs. Recent reports found that RhoA/Rho-kinase (ROCK) pathway is implicated in various fibrogenic diseases. Intradermal injection of hypochlorous acid (HOCl)-generating solution induced inflammation, autoimmune activation, and fibrosis, mimicking the cutaneous diffuse form of SSc in humans. Our study aimed firstly to describe pulmonary inflammation and fibrosis induced by HOCl in mice, and secondly to determine whether fasudil, a selective inhibitor of ROCK, could prevent lung and skin fibroses in HOCl-injected mice. Methods: Female C57BL/6 mice received daily intradermal injection of hypochlorous acid (HOCl) for 6 weeks to induce SSc, with and without daily treatment with fasudil (30 mg·kg⁻¹·day⁻¹) by oral gavage. Results: HOCl intoxication induced significant lung inflammation (macrophages and neutrophils infiltration), and fibrosis. These modifications were prevented by fasudil treatment. Simultaneously, HOCl enhanced ROCK activity in lung and skin tissues. Inhibition of ROCK reduced skin fibrosis, expression of α-smooth-muscle actin and 3-nitrotyrosine, as well as the activity of ROCK in the fibrotic skin of HOCl-treated mice, through inhibition of phosphorylation of Smad2/3 and ERK1/2. Fasudil significantly decreased the serum levels of anti-DNA-topoisomerase-1 antibodies in mice with HOCl-induced SSc. Conclusions: Our findings confirm HOCl-induced pulmonary inflammation and fibrosis in mice, and provide further evidence for a key role of RhoA/ROCK pathway in several pathological processes of experimental SSc. Fasudil could be a promising therapeutic approach for the treatment of SSc.

Background Respiratory failure is a life-threatening and unpredictable complication of systemic sclerosis (SSc). A study was undertaken to assess the value of alveolar nitric oxide (NO) in predicting the risk of lung function deterioration leading to respiratory failure or death in patients with SSc. Methods 105 patients with SSc were enrolled in this prospective cohort and were followed longitudinally over a 3-year period during which the risk of occurrence of deleterious events was analysed according to alveolar concentration (C_Ano), conducting airway output (J′_awno) and fractional concentration (F_Eno_0.05) of exhaled NO measured at inclusion. Comparison was made between each NO parameter to predict the occurrence of deleterious events, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death. Results The area under the receiver operating characteristic curve of C_Ano to predict the occurrence of the combined events was 0.84 (95% CI 0.76 to 0.92; p<0.001), which was significantly higher than those of J′_awno and F_Eno_0.05 (p<0.001). A cut-off of C_Ano of 5.3 ppb had a sensitivity of 88% and a specificity of 62% for the prediction of the occurrence of combined events during follow-up, and was validated in an independent cohort of patients with SSc. Combined events occurred more frequently in patients whose C_Ano was >5.3 ppb. The adjusted HR for patients with C_Ano >5.3 ppb was 6.06 (95% CI 2.36 to 15.53; p<0.001). C_Ano accurately predicted the occurrence of combined events irrespective of forced vital capacity values or the presence of interstitial lung disease at baseline. Conclusions Increased C_Ano accurately identifies patients with SSc with a high risk of developing lung function deterioration and may help to initiate early appropriate treatment.

Objective: Systemic sclerosis (SSc) is characterized by microvascular damage, fibrosis of skin and visceral organs, and autoimmunity. Previous studies have shown that angiotensin II is involved in the synthesis of type I collagen. We investigated whether the blockade of angiotensin II receptor type I (AT₁) by irbesartan reduces skin and lung fibrosis in 2 murine models of SSc.Methods: SSc was induced by daily intradermal injection of HOCl into the backs of BALB/c mice (HOCl‐induced SSc). Mice were treated daily with irbesartan by oral gavage.Results: Irbesartan reduced dermal thickness, collagen concentration, Smad2/3, and α‐smooth muscle actin expression, as well as fibroblast proliferation and H‐Ras expression in the skin of mice with HOCl‐induced SSc. Mice treated with irbesartan also displayed less lung fibrosis, less inflammation, and a lower concentration of collagen in the lungs than untreated mice. Exhaled nitric oxide, inducible nitric oxide synthase, and 3‐nitrotyrosine expression in the lungs were decreased following irbesartan treatment. Moreover, irbesartan reduced the number and the proliferation of splenic B and T cells and the serum levels of anti–DNA topoisomerase I autoantibodies.Conclusion: Irbesartan, an AT₁antagonist, prevents fibrosis and inflammation and inhibits nitric oxide production in HOCl‐induced models of systemic fibrosis. Our findings extend the indication of an AT₁antagonist to SSc patients with diffuse fibrosis, especially those with lung involvement.