Plasma Acute Phase Proteins as Predictors of Chronic Lung Allograft Dysfunction in Lung Transplant Recipients

• Published in: Journal of inflammation research 2020-11, Vol.13, p.1021-1028
• Main Authors: Janciauskiene, Sabina, Royer, Pierre-Joseph, Fuge, Jan, Wrenger, Sabine, Chorostowska-Wynimko, Joanna, Falk, Christine, Welte, Tobias, Reynaud-Gaubert, Martine, Roux, Antoine, Tissot, Adrien, Magnan, Antoine
• Format: Article
• Language: English
• Subjects: Acute phase proteins; Albumin; allograft dysfunction; Antithrombin; Biomarkers; Blood & organ donations; C-reactive protein; Ceruloplasmin; Clinical Trial Report; Infections; Life Sciences; Lung diseases; Lung transplantation; Lung transplants; Medical prognosis; Medical screening; Organ transplant recipients; Patients; Plasma; Prognosis; Proteins; Software; transplantation; Transplantation of organs, tissues, etc; Transplants & implants; Xenografts; α2-Macroglobulin
• ISSN: 1178-7031; 1178-7031
• DOI: 10.2147/JIR.S272662

Cumulating reports suggest that acute phase proteins (APPs) have diagnostic and prognostic value in different clinical conditions. Among others, APPs are proposed to serve as markers that help to control the outcome of transplant recipients. Here, we questioned whether plasma concentrations of APPs mirror the development of chronic lung allograft dysfunction (CLAD). We performed blinded analysis of serial plasma samples retrospectively collected from 35 lung transplanted patients, of whom 25 developed CLAD and 10 remained stable during the follow-up period of 3 to 4.5 years. Albumin (ALB), alpha1-antitrypsin (AAT), high sensitivity C-reactive protein (CRPH), antithrombin-3 (AT3), ceruloplasmin (CER), and alpha2-macroglobulin (A2MG) were measured by the nephelometric method. We found that within the first six months post-transplantation, levels of A2MG, CER and AAT were higher in stable patients relative to those who later developed CLAD. Moreover, in stable patient's plasma CRPH levels decreased during the follow-up period whereas opposite, in those developing CLAD, the CRPH gradually increased. The ALB levels became significantly lower at the end of the follow-up period in CLAD relative to a stable group. A logistic regression model based on A2MG, CER and AT3 at cut-offs levels of [greater than or equal to]175.5 mg/dL, [greater than or equal to]37.8 mg/dL and [greater than or equal to]27.35 mg/dL enabled to discriminate between stable and CLAD patients with a sensitivity of 87.5%, 100% and 62.5%, and specificity of 65.9%, 72.7% and 79.5%, respectively. We identified A2MG (below 175.5 mg/dL) as an independent predictor of CLAD (hazard ratio 11.5, 95% CI (1.5-91.3), p