title: Proteomic demonstration of the recurrent presence of inter-alpha-inhibitor H4 heavy-chain during aspergillosis induced in an animal model.
abstract: Invasive pulmonary aspergillosis remains a matter of great concern in oncology/haematology, intensive care units and organ transplantation departments. Despite the availability of various diagnostic tools with attractive features, new markers of infection are required for better medical care. We therefore looked for potential pulmonary biomarkers of aspergillosis, by carrying out two-dimensional (2D) gel electrophoresis comparing the proteomes of bronchial-alveolar lavage fluids (BALF) from infected rats and from control rats presenting non-specific inflammation, both immunocompromised. A bioinformatic analysis of the 2D-maps revealed significant differences in the abundance of 20 protein spots (ANOVA P-value<0.01; q-value<0.03; power>0.8). One of these proteins, identified by mass spectrometry, was considered of potential interest: inter-alpha-inhibitor H4 heavy-chain (ITIH4), characterised for the first time in this infectious context. Western blotting confirmed its overabundance in all infected BALF, particularly at early stages of murine aspergillosis. Further investigations were carried on rat serum, and confirmed that ITIH4 levels increased during experimental aspergillosis. Preliminary results in human samples strengthened this trend. To our knowledge, this is the first description of the involvement of ITIH4 in aspergillosis.
authors.affiliation: CHU de Tours, Service de Parasitologie - Mycologie - Médecine tropicale, Tours, France; Université François Rabelais, CEPR UMR-INSERM U1100/E.A. 6305, Faculté de Médecine, Tours, France. Electronic address: guillaume.desoubeaux@univ-tours.fr.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Desoubeaux
authors.affiliation: CHU de Tours, Service d'Hématologie Biologique, Tours, France; Université François Rabelais, INSERM U1069/N2C, Faculté de Médecine, Tours, France.
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Jourdan
authors.affiliation: Sysdiag, CNRS UMR 3145 Bio-Rad, Cap Delta, Montpellier, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Valera
authors.affiliation: Sysdiag, CNRS UMR 3145 Bio-Rad, Cap Delta, Montpellier, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Jardin
authors.affiliation: Plateforme de spectrométrie de masse protéomique - MSPP, Laboratoire de Protéomique Fonctionnelle, INRA UR1199, Montpellier, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Hem
authors.affiliation: CHU de Tours, Centre d'Investigation Clinique, Tours, France; Université François Rabelais, INSERM 202, Faculté de Médecine, Tours, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Caille
authors.affiliation: CHU de Tours, Service d'Anatomie et Cytologie Pathologiques, Tours, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Cormier
authors.affiliation: Université François Rabelais, CEPR UMR-INSERM U1100/E.A. 6305, Faculté de Médecine, Tours, France; CHU de Tours, Service de Pneumologie, Tours, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Marchand-Adam
authors.affiliation: CHU de Tours, Service de Parasitologie - Mycologie - Médecine tropicale, Tours, France.
authors.forename: Éric
authors.initials: É
authors.lastname: Bailly
authors.affiliation: Université François Rabelais, CEPR UMR-INSERM U1100/E.A. 6305, Faculté de Médecine, Tours, France; CHU de Tours, Service de Pneumologie, Tours, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Diot
authors.affiliation: CHU de Tours, Service de Parasitologie - Mycologie - Médecine tropicale, Tours, France; Université François Rabelais, CEPR UMR-INSERM U1100/E.A. 6305, Faculté de Médecine, Tours, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Chandenier
mesh_terms: D000510:Alpha-Globulins / Q000032:analysis*; D000818:Animals; D001228:Aspergillosis / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis* / Q000097:blood; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D008297:Male; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000737:chemistry
chemical_list: D000510:Alpha-Globulins; D015415:Biomarkers; C011877:inter-alpha-inhibitor
keywords: Bronchial-alveolar lavage; Invasive pulmonary aspergillosis; Mass spectrometry; Proteomics; Rat model; Statistical analysis; Two-dimensional gel electrophoresis