Biomarkers for Chronic Lung Allograft Dysfunction: Ready for Prime Time?

Abstract

Chronic lung allograft dysfunction (CLAD) remains a major hurdle impairing lung transplant outcome. Parallel to the better clinical identification and characterization of CLAD and CLAD phenotypes, there is an increasing urge to find adequate biomarkers that could assist in the earlier detection and differential diagnosis of CLAD phenotypes, as well as disease prognostication. The current status and state-of-the-art of biomarker research in CLAD will be discussed with a particular focus on radiological biomarkers or biomarkers found in peripheral tissue, bronchoalveolar lavage‚ and circulating blood‚ in which significant progress has been made over the last years. Ultimately, although a growing number of biomarkers are currently being embedded in the follow-up of lung transplant patients, it is clear that one size does not fit all. The future of biomarker research probably lies in the rigorous combination of clinical information with findings in tissue, bronchoalveolar lavage‚ or blood. Only by doing so, the ultimate goal of biomarker research can be achieved, which is the earlier identification of CLAD before its clinical manifestation. This is desperately needed to improve the prognosis of patients with CLAD after lung transplantation.

Chronic Lung Allograft Dysfunction, a Review in 2023

“…Transbronchial lung biopsies are typically performed to assess for evidence of acute cellular or antibody mediated rejection as routine surveillance or in patients with worsening lung function. Identifying CLAD with transbronchial biopsies has a low yield, but findings such as organizing pneumonia and bronchial eosinophilia can suggest CLAD in the appropriate clinical context [33].…”

“…In addition, circulating donor specific antibodies have been linked to the developing of acute rejection and CLAD. Persistence of high levels of donor specific antibodies has been associated with the RAS phenotype in particular [33]. Plasma levels of donor-derived cell free DNA (dd-cfDNA) from the lung allograft increase during episodes of rejection, and thresholds with high sensitivity and negative predictive value have been established to detect rejection, even in asymptomatic patients [28].…”

Molecular monitoring of lung allograft health: is it ready for routine clinical use?

“…Numerous publications have analysed different immune cell profiles and their connection to lung allograft dysfunction [109][110][111]. BROSSEAU et al [110] demonstrated that LTRs with a frequency of CD9 + B-cells below 6.6% in peripheral blood had a significantly higher incidence of BOS.…”

Cellular Biomarkers of Rejection in Lung Transplant: The Usefulness of Eosinophil and Lymphocyte Counts

“…Peripheral blood is an easily accessible biological sample frequently used in the search for the "ideal biomarker". Multiple studies have tried to identify biomarkers of rejection in peripheral blood for the early diagnosis of ACR and CLAD [15][16] . In this regard, we can highlight, amongst others, the determination of several cytokines and chemokines, KL6, exosomes, or donor-derived cell-free DNA.…”