C-C Motif Chemokine Ligand 15 May Be a Useful Biomarker for Predicting the Prognosis of Patients with Chronic Hypersensitivity Pneumonitis

Respiration. 2019;98(3):212-220. doi: 10.1159/000500576. Epub 2019 Aug 15.

Abstract

Background: Chronic hypersensitivity pneumonitis (CHP) is characterized by lymphocytic inflammation and progressive fibrosis of the lung caused by a variety of inhaled antigens. Due to the difficulty of accurately diagnosing CHP, and the poor prognosis associated with the condition, a novel clinical biomarker is urgently needed.

Objective: To investigate the usefulness of C-C motif chemokine ligand 15 (CCL15), which had been demonstrated to highly express in the lungs of CHP patients, as a clinical biomarker for CHP.

Method: Immunohistochemical investigations were performed on lung tissue from CHP patients, and CCL15 levels in serum and bronchoalveolar lavage fluid (BALF) were measured via the enzyme-linked immunosorbent assay.

Results: Immunohistochemistry investigations revealed high CCL15 expression in the lungs of CHP patients. Serum CCL15 levels in CHP patients (29.1 ± 2.1 μg/mL) were significantly higher than those of idiopathic pulmonary fibrosis patients (19.7 ± 1.3 μg/mL, p = 0.01) and healthy subjects (19.5 ± 1.7 μg/mL, p = 0.003). When BALF CCL15 level was divided by BALF albumin (Alb) level (BALF CCL15/Alb), it was significantly inversely correlated with forced vital capacity (β = -0.47, p = 0.0006), percentage of predicted carbon monoxide diffusion capacity of the lung (β = -0.41, p = 0.0048), and BALF lymphocyte count (β = -0.34, p = 0.01) in CHP patients. Multivariate Cox proportional hazards analysis revealed that high BALF CCL15/Alb and poor prognosis were statistically significantly independently correlated in CHP patients (HR 1.1, 95% CI 1.03-1.18, p = 0.004).

Conclusion: The results of the current study suggest that CCL15 may be a useful prognostic biomarker for CHP. CCL15 was highly expressed in the lung tissue of CHP patients, and BALF CCL15/Alb was significantly associated with CHP prognosis.

Keywords: Bronchoalveolar lavage fluid C-C motif chemokine ligand 15; Enzyme-linked immunosorbent assay; Prognostic biomarker.

MeSH terms

  • Aged
  • Albumins / metabolism
  • Alveolitis, Extrinsic Allergic / metabolism*
  • Alveolitis, Extrinsic Allergic / physiopathology
  • Biopsy
  • Bronchoalveolar Lavage Fluid / chemistry
  • Case-Control Studies
  • Chemokines, CC / metabolism*
  • Chronic Disease
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Idiopathic Pulmonary Fibrosis / metabolism*
  • Immunohistochemistry
  • Lung / metabolism*
  • Macrophage Inflammatory Proteins / metabolism*
  • Macrophages, Alveolar / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Plasma Cells / metabolism
  • Prognosis
  • Proportional Hazards Models
  • Pulmonary Diffusing Capacity
  • Severity of Illness Index
  • Vital Capacity

Substances

  • Albumins
  • CCL15 protein, human
  • Chemokines, CC
  • Macrophage Inflammatory Proteins