A High Level of Soluble CD40L Is Associated with P. aeruginosa Infection in Patients with Cystic Fibrosis

PLoS One. 2016 Dec 28;11(12):e0168819. doi: 10.1371/journal.pone.0168819. eCollection 2016.

Abstract

Objective: The aim of this study was to evaluate whether the concentration of sCD40L, a product of platelet activation, correlates with the presence of Pseudomonas aeruginosa in the airway of patients with cystic fibrosis (CF) and to determine its possible clinical association.

Methods: Sixty patients with CF, ranging in age from 2 months to 36 years, were studied. The demographics, cystic fibrosis transmembrane conductance regulator (CFTR) genotype, spirometry measurements, radiographic and tomographic scans, platelet count in peripheral blood, sCD40L, IL-6, TNF-α and ICAM1 data were collected. Infection-colonization of the airway was evaluated using sputum and throat swab cultures; the levels of anti-Pseudomonas aeruginosa antibodies (Anti-PaAb) were evaluated.

Results: Patients with CF and chronic colonization had anti-PaAb values of 11.6 ± 2.1 ELISA units (EU) and sCD40L in plasma of 1530.9 ±1162.3 pg/mL; those with intermittent infection had 5.7 ± 2.7 EU and 2243.6 ± 1475.9 pg/mL; and those who were never infected had 3.46 ± 1.8 EU (p≤0.001) and 1008.1 ± 746.8 pg/mL (p≤0.01), respectively. The cutoff value of sCD40L of 1255 pg/mL was associated with an area under the ROC (receiver operating characteristic curve) of 0.84 (95% CI, 0.71 to 0.97), reflecting P. aeruginosa infection with a sensitivity of 73% and a specificity of 89%. Lung damage was determined using the Brasfield Score, the Bhalla Score, and spirometry (FVC%, FEV1%) and found to be significantly different among the groups (p≤0.001).

Conclusion: Circulating sCD40L levels are increased in patients with cystic fibrosis and P. aeruginosa infection. Soluble CD40L appears to reflect infection and provides a tool for monitoring the evolution of lung deterioration.

MeSH terms

  • Adolescent
  • CD40 Ligand / blood*
  • CD40 Ligand / chemistry*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cystic Fibrosis / blood*
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / microbiology*
  • Female
  • Humans
  • Infant
  • Male
  • Pseudomonas Infections / complications*
  • Pseudomonas aeruginosa / physiology*
  • ROC Curve
  • Solubility
  • Young Adult

Substances

  • CD40 Ligand

Grants and funding

The authors received no specific funding for this work.