title: Proinflammatory isoforms of IL-32 as novel and robust biomarkers for control failure in HIV-infected slow progressors.
abstract: HIV-infected slow progressors (SP) represent a heterogeneous group of subjects who spontaneously control HIV infection without treatment for several years while showing moderate signs of disease progression. Under conditions that remain poorly understood, a subgroup of these subjects experience failure of spontaneous immunological and virological control. Here we determined the frequency of SP subjects who showed loss of HIV control within our Canadian Cohort of HIV(+) Slow Progressors and identified the proinflammatory cytokine IL-32 as a robust biomarker for control failure. Plasmatic levels of the proinflammatory isoforms of IL-32 (mainly β and γ) at earlier clinic visits positively correlated with the decline of CD4 T-cell counts, increased viral load, lower CD4/CD8 ratio and levels of inflammatory markers (sCD14 and IL-6) at later clinic visits. We present here a proof-of-concept for the use of IL-32 as a predictive biomarker for disease progression in SP subjects and identify IL-32 as a potential therapeutic target.
authors.affiliation: CHUM-Research Centre, Montréal, QC, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Far
authors.affiliation: CHUM-Research Centre, Montréal, QC, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de, Montréal, QC, Canada.
authors.forename: Pascale
authors.initials: P
authors.lastname: Kouassi
authors.affiliation: CHUM-Research Centre, Montréal, QC, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Sylla
authors.affiliation: CHUM-Research Centre, Montréal, QC, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de, Montréal, QC, Canada.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: CHUM-Research Centre, Montréal, QC, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Fouda
authors.affiliation: CHUM-Research Centre, Montréal, QC, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de, Montréal, QC, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fabre
authors.affiliation: Caprion, Montréal, QC, Canada.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Goulet
authors.affiliation: INRS-Institut Armand Frappier, Laval, QC, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: van Grevenynghe
authors.affiliation: CIHR Canadian HIV Trials Network, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Terry
authors.initials: T
authors.lastname: Lee
authors.affiliation: CIHR Canadian HIV Trials Network, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Singer
authors.affiliation: AIDS Research Program, St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Marianne
authors.initials: M
authors.lastname: Harris
authors.affiliation: Clinique Médicale Quartier Latin, Montréal, QC, Canada.
authors.forename: Jean-Guy
authors.initials: JG
authors.lastname: Baril
authors.affiliation: Clinique Médicale l'Actuel, Montréal, QC, Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: Trottier
authors.affiliation: CHUM-Research Centre, Montréal, QC, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de, Montréal, QC, Canada.
authors.forename: Petronela
authors.initials: P
authors.lastname: Ancuta
authors.affiliation: Division of Hematology and Chronic Viral Illness Service, McGill University Health Centre, Montréal, QC, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.affiliation: Research Institute, McGill University Health Centre, Montréal, QC, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bernard
authors.affiliation: CHUM-Research Centre, Montréal, QC, Canada.|Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université de, Montréal, QC, Canada.
authors.forename: Cécile L
authors.initials: CL
authors.lastname: Tremblay
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D015331:Cohort Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015658:HIV Infections / Q000097:blood* / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007378:Interleukins / Q000097:blood* / Q000235:genetics; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D019562:Viral Load / Q000276:immunology
chemical_list: D015415:Biomarkers; C496971:IL32 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D007378:Interleukins; D018950:Lipopolysaccharide Receptors; D020033:Protein Isoforms