Involvement of IL-26 in bronchiolitis obliterans syndrome but not in acute rejection after lung transplantation

Abstract

Background The main long-term complication after lung transplantation is bronchiolitis obliterans syndrome (BOS), a deadly condition in which neutrophils may play a critical pathophysiological role. Recent studies show that the cytokine interleukin IL-26 can facilitate neutrophil recruitment in response to pro-inflammatory stimuli in the airways. In this pilot study, we characterized the local involvement of IL-26 during BOS and acute rejection (AR) in human patients. Method From a biobank containing bronchoalveolar lavage (BAL) samples from 148 lung transplant recipients (LTR), clinically-matched patient pairs were identified to minimize the influence of clinical confounders. We identified ten pairs (BOS/non-BOS) with BAL samples harvested on three occasions for our longitudinal investigation and 12 pairs of patients with and without AR. The pairs were matched for age, gender, preoperative diagnosis, type of and time after surgery. Extracellular IL-26 protein was quantified in cell-free BAL samples using an enzyme-linked immunosorbent assay. Intracellular IL-26 protein in BAL cells was determined using immunocytochemistry (ICC) and flow cytometry. Results The median extracellular concentration of IL-26 protein was markedly increased in BAL samples from patients with BOS (p < 0.0001) but not in samples from patients with AR. Intracellular IL-26 protein was confirmed in alveolar macrophages and lymphocytes (through ICC and flow cytometry) among BAL cells obtained from BOS patients. Conclusions Local IL-26 seems to be involved in BOS but not AR, and macrophages as well as lymphocytes constitute cellular sources in this clinical setting. The enhancement of extracellular IL-26 protein in LTRs with BOS warrants further investigation of its potential as a target for diagnosing, monitoring, and treating BOS.

Worldwide Bronchiolitis obliterans research: A bibliometric analysis of the published literature between 2002 and 2022

“…[ 37 ] Plasma levels of CRH, FERC2, IL-20RA, TNFB, and IGSF3 are significantly lower in patients with BOS, whereas MMP-9, CTSL1, and IL-26 are elevated, and these indicators are expected to provide a basis for the diagnosis and identification of BOS. [ 38 , 39 ] Histopathologically, patients with BOS patients have different characteristics than non-CLAD patients in terms of exoskeletal lung tissue: patients with confirmed BOS have significant histological lesions, mainly centered in the airways; significant vascular lesions in BOS; fibrotic changes in BOS; and non-CLAD patients exhibit airway-centered lesions with lesser degrees of vascular lesions and fibrotic changes. [ 36 ] BOS after HSCT triggers systemic graft-versus-host disease (GVHD), and the effects of BOS after LT are limited to lung allografts, the former being more challenging to diagnose.…”