title: Ro52/TRIM21-deficient expression and function in different subsets of peripheral blood mononuclear cells is associated with a proinflammatory cytokine response in patients with idiopathic inflammatory myopathies.
abstract: The presence of anti-Ro52/tripartite motif 21 (Trim21) autoantibodies has been associated with a distinctive clinical profile and has gained value as a prognostic marker in idiopathic inflammatory myopathies (IIM). The aim of the present work was to analyse Ro52/Trim21 expression in different subsets of peripheral blood mononuclear cells (PBMCs) of patients with IIM, as well as the ubiquitination profile and its association with proinflammatory cytokine production. We included 18 patients with recent-onset IIM and 18 age- and gender-matched healthy donors. PBMCs were isolated and different subsets (CD4+, CD8+, CD14+) were purified by magnetic selection. The expression of Ro52/Trim21 in different PBMC subsets of patients with IIM and healthy donors was analysed by Western blot. We assessed the presence of myositis-specific and associated autoantibodies by enzyme-linked immunosorbent assay (ELISA). Cytokine levels were measured by cytometric bead array. Patients with IIM showed decreased protein expression of Ro52/Trim21 in comparison to healthy controls in PBMC (0·97 ± 0·60 versus 1·84 ± 0·92, P = 0·016), CD4+lymphocytes (0·79 ± 0·54 versus 2·41 ± 0·78, P = 0·017), and monocytes (0·87 ± 0·35 versus 1·89 ± 0·20, P < 0·001). There were no significant differences among IIM groups. Also, a lower K48-mediated ubiquitination profile was found, predominantly in CD4+lymphocytes. Furthermore, after mitogenic stimulation, there was a higher synthesis of proinflammatory cytokines by T cells [interleukin (IL)-17A and tumour necrosis factor (TNF)-α] and monocytes [IL-6 and interferon (IFN)-α] from IIM patients compared with healthy controls. Our data suggest that patients with IIM, mainly DM, are characterized by a deficient expression of Ro52/TRIM21 in different PBMC subsets (CD4+lymphocytes and monocytes), along with lower K48-mediated ubiquitination, which is associated with a proinflammatory cytokine response.
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico.
authors.forename: D
authors.initials: D
authors.lastname: Gómez-Martín
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico.
authors.forename: A S
authors.initials: AS
authors.lastname: Galindo-Feria
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Barrera-Vargas
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Merayo-Chalico
authors.affiliation: Research Support Network, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán-Universidad Nacional Autónoma de México (CIC-UNAM), Mexico City, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Juárez-Vega
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Torres-Ruiz
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Alcocer-Varela
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000172:deficiency*; D054875:Ubiquitination; D000099207:SS-A Antigen
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D012261:Ribonucleoproteins; D000099207:SS-A Antigen
keywords: Ro52; Trim21; idiopathic inflammatory myopathies; peripheral blood mononuclear cells