Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis.

Decision on treatment of systemic sclerosis (SSc) related interstitial lung disease (ILD) largely relies on the findings on high resolution computed tomography (HRCT) and there is a need for improvement in assessment of the fibrotic activity. The objectives of this study were to study biomarkers in bronchoalveolar lavage fluid (BALF) from SSc patients with ILD and to relate the findings to the severity and activity of lung fibrosis. Fifteen patients with early SSc and 12 healthy controls were subjected to BAL. Cell counts and analyses of CXCL5, CXCL8 and S100A8/A9 were performed in BALF and serum. COMP and KL-6 were measured in serum. HRCT of lungs was quantified for ground glass opacities (GGO), reticulation and traction bronchiectases. BALF concentrations of CXCL8 (p < 0.001), CXCL5 (p = 0.002) and S100A8/A9 (p = 0.016) were higher in patients than controls. Serum KL-6 (p < 0.001) was increased in SSc patients and correlated with BALF concentration of eosinophils (rS = 0.57, p = 0.027). Patients with more widespread GGO on HRCT were characterised in BALF by a higher eosinophil count (p = 0.002) and in serum by higher KL-6 (p = 0.008). Patients with more fibrosis were characterised in BALF by higher eosinophil count (p = 0.014), higher CXCL8 (p = 0.005) and S100A8A/A9 (p = 0.014) concentration and in serum by a higher serum COMP (p = 0.023). In SSc related ILD, biomarkers from BALF and serum correlate to findings on HRCT suggesting usefulness as markers of presence and extent of lung fibrosis.

Hesselstrand R ，Wildt M ，Bozovic G ，Andersson-Sjöland A ，Andréasson K ，Scheja A ，Westergren-Thorsson G ，Bjermer L ，Wuttge DM ... -  《-》

Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease.

Benyamine A ，Heim X ，Resseguier N ，Bertin D ，Gomez C ，Ebbo M ，Harlé JR ，Kaplanski G ，Rossi P ，Bardin N ，Granel B ... -  《-》

CXCL11 in bronchoalveolar lavage fluid and pulmonary function decline in systemic sclerosis.

Sfriso P ，Cozzi F ，Oliviero F ，Caso F ，Cardarelli S ，Facco M ，Fittà C ，Del Rosso A ，Matucci-Cerinic M ，Punzi L ，Agostini C ... -  《CLINICAL AND EXPERIMENTAL RHEUMATOLOGY》

Association of elevated α-defensin levels with interstitial pneumonia in patients with systemic sclerosis.

Sakamoto N ，Kakugawa T ，Hara A ，Nakashima S ，Yura H ，Harada T ，Ishimoto H ，Yatera K ，Kuwatsuka Y ，Hara T ，Ichinose K ，Obase Y ，Ishimatsu Y ，Kohno S ，Mukae H ... -  《RESPIRATORY RESEARCH》

Performance of Candidate Serum Biomarkers for Systemic Sclerosis-Associated Interstitial Lung Disease.

Interstitial lung disease (ILD) in systemic sclerosis (SSc) runs a highly variable course, and prediction tools are highly desired. The aim of this study was to assess the diagnostic and prognostic performance of 4 candidate serum biomarkers for SSc-associated ILD. Serum samples from a combined cohort of SSc patients (from Paris, France and Oslo, Norway; n = 427) were analyzed by enzyme-linked immunosorbent assay for concentrations of lung epithelial-derived surfactant protein D (SP-D), Krebs von den Lungen 6 glycoprotein (KL-6), CCL18, and OX40 ligand (OX40L). Lung fibrosis was measured by high-resolution computed tomography and pulmonary function tests. Associations of these candidate biomarkers with baseline disease involvement and prediction of disease progression over time (mean ± SD follow-up 3.2 ± 4.4 years) were investigated. In SSc patients at baseline, serum levels of KL-6 correlated with the forced vital capacity (FVC) (r = -0.317, P < 0.001), diffusing capacity for carbon monoxide (r = -0.335, P < 0.001), and extent of lung fibrosis (r = 0.551, P < 0.001). In multivariate analyses, serum levels of KL-6 and SP-D, but not CCL18 and OX40L, were associated with lung fibrosis (odds ratio [OR] 2.41, 95% confidence interval [95% CI] 1.43-4.07 [P = 0.001] and OR 3.15, 95% CI 1.81-5.48 [P < 0.001], respectively). In SSc patients with ILD at baseline, longitudinal, multivariate analyses showed that CCL18 serum levels were an independent predictor of a >10% decrease in the FVC (hazard ratio [HR] 2.90, 95% CI 1.25-6.73; P = 0.014) and de novo development of extensive disease (HR 3.71, 95% CI 1.02-13.52; P = 0.048). Matrix-based logistic regression models for the diagnosis and prognosis of SSc-associated ILD were constructed, and these models discriminated 3 groups of risk (mild, moderate, or high) for the diagnosis or worsening of lung fibrosis according to the serum levels of SP-D (for diagnosis) and serum levels of CCL18 (for progression of disease). These results show that SP-D is a relevant diagnostic biomarker for SSc-associated ILD, whereas KL-6 could be used to assess the severity of lung fibrosis. CCL18 appears to be a potential predictive marker for progression of ILD in SSc.

Elhai M ，Hoffmann-Vold AM ，Avouac J ，Pezet S ，Cauvet A ，Leblond A ，Fretheim H ，Garen T ，Kuwana M ，Molberg Ø ，Allanore Y ... -  《-》