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

Dis Markers. 2020 May 12:2020:2696173. doi: 10.1155/2020/2696173. eCollection 2020.

Abstract

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.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Axl Receptor Tyrosine Kinase
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Female
  • Gene Expression Regulation
  • Humans
  • Hypertension, Pulmonary / blood
  • Hypertension, Pulmonary / complications
  • Hypertension, Pulmonary / diagnosis*
  • Hypertension, Pulmonary / genetics
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Lung Diseases, Interstitial / blood
  • Lung Diseases, Interstitial / complications
  • Lung Diseases, Interstitial / diagnosis*
  • Lung Diseases, Interstitial / genetics
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / blood
  • Proto-Oncogene Proteins / genetics*
  • Receptor Protein-Tyrosine Kinases / blood
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / diagnosis*
  • Scleroderma, Systemic / genetics
  • Sensitivity and Specificity
  • Severity of Illness Index
  • c-Mer Tyrosine Kinase / blood
  • c-Mer Tyrosine Kinase / genetics*

Substances

  • Biomarkers
  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins
  • growth arrest-specific protein 6
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human