Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders.

BACKGROUND: Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). AIMS: To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications of SS and SSD. METHODS: In a cross-sectional observational study, we recruited 125 consecutive patients, affected by SS and SSD and referred to a tertiary-level pulmonary hypertension outpatient clinic. All patients underwent a comprehensive evaluation for identification of PAH and ILD. Gas6, sMer, and sAxl concentrations were measured with ELISA protocols, and concentrations were compared according to PAH or ILD. RESULTS: Nineteen subjects had pulmonary hypertension (PH) (14 PAH), and 39 had ILD (6 severe). Plasma sMer was increased in PAH (18.6 ng/ml IQR [11.7-20.3]) with respect to the absence (12.4 [8.0-15.8]) or other form of pulmonary hypertension (9.6 [7.4-12.5]; K-W variance p < 0.04). Conversely, Gas6 and sAxl levels were slightly increased in mild ILD (25.8 ng/ml [19.5-32.1] and 24.6 [20.1-32.5]) and reduced in severe ILD (16.6 [15.0-22.1] and 15.5 [14.9-22.4]) in comparison to no evidence of ILD (23.4 [18.8-28.1] and 21.6 [18.1-28.4]; K-W, p ≤ 0.05). Plasma sMer ≥ 19 ng/ml has 50% sensitivity and 92% specificity in PAH identification (area under the ROC curve (AUC) 0.697, p < 0.03). Values of Gas6 ≤ 24.5 ng/ml and of sAxl ≤ 15.5 ng/ml have 100% and 67% sensitivity and 47% and 86% specificity, respectively, in identifying severe ILD (Gas6 AUC 0.787, p < 0.001; sAxl AUC 0.705, p < 0.05). CONCLUSIONS: The assay of Gas6 sAxl and sMer may be useful to help in the identification of PAH and ILD in SS and SSD patients. The Gas6/TAM system seems to be relevant in cardiopulmonary complications of SS and SSD and merits further investigations.

Red Cell Distribution Width and Platelet Count as Biomarkers of Pulmonary Arterial Hypertension in Patients with Connective Tissue Disorders.

INTRODUCTION/OBJECTIVE: In the present paper, we aimed to test the value of the red cell distribution width (RDW) coefficient of variation as a candidate biomarker for pulmonary arterial hypertension (PAH) in patients with connective tissue disorders (CTD), correlating it with the degree of cardiopulmonary impairment in these patients. METHODS: The study population included N = 141 patients with CTD and N = 59 patients affected by pulmonary hypertension of other etiologies, all referred to the Pulmonary Hypertension Clinic of the Cardiology Division of an Academic Hospital in Northern Italy for evaluation (including right catheterization). Clinical, instrumental, and laboratory data were collected and related to RDW and other full blood count indexes. RESULTS: Twenty out of 141 CTD patients (14%) received a diagnosis of PAH. In comparison to those without PAH, CTD patients with PAH displayed a larger RDW (14.9% (13.5-17.2) vs. 13.8% (13.1-15.0); p = 0.02) and a lower platelet count (205 (177-240) × 109/l vs. 244 (197.5-304.2) × 109/l; p = 0.005). Moreover, with respect to CTD patients without PAH, RDW was significantly larger also in PH of other etiologies. In contrast, the platelet count was significantly lower only in CTD-related PAH, with a value > 276 × 109/l being 100% sensitive in ruling out PAH. Finally, RDW, but not the platelet count, was related directly to systolic pulmonary arterial pressure (r = 0.381; p = 0.0008) and right ventricle diameter (r = 0.283; p = 0.015) and inversely to diffusing capacity of the lung for carbon monoxide (r = -0.325; p = 0.014). CONCLUSION: RDW is a promising candidate biomarker for the screening and the prognostic stratification of PAH in CTD patients.