title: Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies.
abstract: Growth arrest and DNA damage-inducible gene 34 (GADD34) is an inducible cofactor of protein phosphatase 1, which has an important role in the unfolded protein response. GADD34 has been shown to be necessary for type I interferon and proinflammatory cytokine production in response to viral infection in murine models. We investigate the expression of GADD34 in rheumatoid arthritis (RA), in which proinflammatory cytokines have an important pathogenic role. The objective of this study was to evaluate the potential of GADD34 expression as a biomarker in RA patients. We report a case-control study on GADD34 gene expression in peripheral blood mononuclear cells of patients (n = 75) with RA and age- and sex-matched healthy controls (n = 25). The study was approved by the relevant local ethics committees. GADD34 gene expression level in peripheral blood mononuclear cells was measured by quantitative PCR and analyzed with Mann-Whitney test. The relation between GADD34 gene overexpression and clinical or biological characteristics was analyzed with univariate and multivariate analysis. GADD34 gene expression was significantly higher in RA patients compared with healthy controls (p ≤ 0.001). Interestingly, GADD34 overexpression in PBMC of patients was related to the presence of circulating anti-citrullinated protein antibodies (p = 0.030). Data of this study strengthen the evidence of an unfolded protein response during the course of RA and provide an insight of the potential interest in GADD34 as a relevant marker for RA.
authors.affiliation: a Laboratoire d'Immunologie , Pôle de Biologie, Grenoble University Hospital , Grenoble , France .|b Laboratoire d'Adaptation et Pathogénie des Microorganismes , UMR5163, CNRS-Université Joseph Fourier , Grenoble , France .
authors.forename: Giovanna
authors.initials: G
authors.lastname: Clavarino
authors.affiliation: a Laboratoire d'Immunologie , Pôle de Biologie, Grenoble University Hospital , Grenoble , France .
authors.forename: Souad
authors.initials: S
authors.lastname: Adriouach
authors.affiliation: c Direction de la Recherche Clinique et de l'Innovation , Pôle Recherche .
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Quesada
authors.affiliation: d Clinique Universitaire de Rhumatologie .
authors.forename: Marine
authors.initials: M
authors.lastname: Clay
authors.affiliation: d Clinique Universitaire de Rhumatologie .
authors.forename: Maxime
authors.initials: M
authors.lastname: Chevreau
authors.affiliation: e Laboratoire de Biochimie des enzymes et des protéines , Pôle de Biologie, Grenoble University Hospital , Grenoble , France , and.
authors.forename: Candice
authors.initials: C
authors.lastname: Trocmé
authors.affiliation: d Clinique Universitaire de Rhumatologie .
authors.forename: Laurent
authors.initials: L
authors.lastname: Grange
authors.affiliation: d Clinique Universitaire de Rhumatologie .
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaudin
authors.affiliation: f Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2 , Inserm U1104, CNRS UMR7280, 13288 Marseille , France.
authors.forename: Evelina
authors.initials: E
authors.lastname: Gatti
authors.affiliation: f Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2 , Inserm U1104, CNRS UMR7280, 13288 Marseille , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pierre
authors.affiliation: a Laboratoire d'Immunologie , Pôle de Biologie, Grenoble University Hospital , Grenoble , France .|b Laboratoire d'Adaptation et Pathogénie des Microorganismes , UMR5163, CNRS-Université Joseph Fourier , Grenoble , France .
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cesbron
authors.affiliation: a Laboratoire d'Immunologie , Pôle de Biologie, Grenoble University Hospital , Grenoble , France .|b Laboratoire d'Adaptation et Pathogénie des Microorganismes , UMR5163, CNRS-Université Joseph Fourier , Grenoble , France .
authors.forename: Chantal
authors.initials: C
authors.lastname: Dumestre-Pérard
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D016017:Odds Ratio; D054645:Protein Phosphatase 1 / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C087519:PPP1R15A protein, human; D054645:Protein Phosphatase 1
keywords: ACPA; RA; endoplasmic reticulum stress; growth arrest and DNA damage-inducible gene 34; protein phosphatase 1 subunit Ppp1r15a