Differential protein expression in endothelial cells exposed to serum from patients with acute graft-vs-host disease, depending on steroid response
Martinez-Sanchez, Julia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Palomo, Marta (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Pedraza, Alexandra (Hospital Clínic i Provincial de Barcelona)
Moreno-Castaño, Ana Belén (Hospital Clínic i Provincial de Barcelona)
Torramade-Moix, Sergi (Hospital Clínic i Provincial de Barcelona)
Rovira, Montserrat (Hospital Clínic i Provincial de Barcelona)
Salas, María Queralt (Hospital Clínic i Provincial de Barcelona)
Cid, Joan (Hospital Clínic i Provincial de Barcelona)
Escolar, Ginès (Hospital Clínic i Provincial de Barcelona)
Penack, Olaf (Universität zu Berlin)
Carreras, Enric (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Diaz-Ricart, Maribel (Hospital Clínic i Provincial de Barcelona)

Date:	2023
Abstract:	Graft-versus-host disease (GVHD) is a complication of allogeneic haematopoietic cell transplantation. Endothelial injury is crucial as pathophysiological substrate for GVHD. GVHD first-line treatment is high-dose corticosteroids, although some patients are steroid-refractory. Through the present study, we compared the endothelial proteomic profiles in response to serum from steroid-refractory acute GVHD (SR-aGVHD) and steroid-sensitive acute GVHD (SS-aGVHD) patients. Blood samples from SR-aGVHD (n = 4) and SS-aGVHD (n = 8) patients were collected at aGVHD diagnosis. Endothelial cell cultures were exposed (48 h) to patients' serum. Protein extraction and proteomic analysis were performed. Differences were statistically evaluated by multivariate analysis. Forty-four proteins contributed to separate all samples into the two study groups, among which 15 participated significantly (p < 0. 05), 10 exhibiting a fold change >1. 2. Differentially expressed proteins were mainly associated with oxidative phosphorylation (Cytochrome C oxidase subunit 6B1, CX6B1), inflammation and angiogenesis (Apolipoprotein D, APOD), cell survival (Rapamycin-insensitive companion of mTOR, RICTR), and oxidative stress (Riboflavin kinase, RIFK). This pilot study used a novel approach to distinguish the aGVHD response to steroid treatment. The proteins differentially expressed could constitute potential biomarkers for steroid-treatment response. These findings signify a step forward to identify the mechanisms of response to steroids, of high clinical relevance considering the SR-aGVHD elevated mortality.
Grants:	Instituto de Salud Carlos III PI19/00888
Note:	Altres ajuts: Fundació La Marató de TV3 (202026-10); Deutsche Forschungsgemeinschaft, Grant/Award Number: PE 1450/7-1 and PE 1450/9-1; Deutsche Krebshilfe, Grant/Award Number: 70113519
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Agvhd ; Endothelial damage biomarkers ; Endothelium ; Proteomic analysis ; Steroid-refractory
Published in:	Journal of Cellular and Molecular Medicine, Vol. 27 Núm. 9 (may 2023) , p. 1227-1238, ISSN 1582-4934

DOI: 10.1111/jcmm.17712
PMID: 37016544

12 p, 7.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles