Corticotropin releasing hormone as an identifier of bronchiolitis obliterans syndrome

Abstract

Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a minimally invasive biomarker of BOS. Here, 644 different proteins were analyzed to detect biomarkers that distinguish BOS grade 0 from grades 1–3. The plasma of 46 double lung transplant patients was analyzed for proteins using a high-component, multiplex immunoassay that enables analysis of protein biomarkers. Proximity Extension Assay (PEA) consists of antibody probe pairs which bind to targets. The resulting polymerase chain reaction (PCR) reporter sequence can be quantified by real-time PCR. Samples were collected at baseline and 1-year post transplantation. Enzyme-linked immunosorbent assay (ELISA) was used to validate the findings of the PEA analysis across both time points and microarray datasets from other lung transplantation centers demonstrated the same findings. Significant decreases in the plasma protein levels of CRH, FERC2, IL-20RA, TNFB, and IGSF3 and an increase in MMP-9 and CTSL1 were seen in patients who developed BOS compared to those who did not. In this study, CRH is presented as a novel potential biomarker in the progression of disease because of its decreased levels in patients across all BOS grades. Additionally, biomarkers involving the remodeling of the extracellular matrix (ECM), such as MMP-9 and CTSL1, were increased in BOS patients.

Comparative Assessment of Acute Pulmonary Effects Induced by Heated Tobacco (IQOS) Aerosol Inhalation in a Murine Model

“…During the reaction, a proximity-dependent DNA polymerization event occurred between a pair of oligonucleotide-labeled antibodies targeting the protein of interest, leading to the generation of a PCR reporter sequence, which was then measured using real-time PCR 14,15 . Internal, extension, and detection controls were utilized to monitor deviations, as outlined by the manufacturer (www.olink.com).…”

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.…”