title: Elevated circulating levels of IL-21 and IL-22 define a cytokine signature profile in type 2 autoimmune hepatitis patients.
abstract: Background and aims. Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver in which the immunological mechanisms involved in tissue destruction and/or repair are still unclear. Different pro-inflammatory cytokines have been shown to play a determinant role in AIH pathogenesis. Here, we aim to compare the circulating levels of pro- and anti-inflammatory cytokines such as IL-6, TNF-?, IL-17A/F, IL-21, IL-22, IL-23, and IL-10 in patients with type 2 AIH compared to patients with type 1 AIH and healthy controls (HC). Fourty-six Mexican patients with AIH were recruited in our study. Patients were classified as type 1 or 2 AIH based on immune serological markers. Fourty-four serum samples from healthy individuals were included as controls. Serum cytokine levels were determined by ELISA technique.
  
  
  RESULTS
  Compared to healthy controls, serum levels of IL-17F, IL-21, IL-23, IL-10, IL-6, and TNF-?, but not IL-17A and IL-22, were significantly increased in AIH patients. When patients were grouped by aminotransferase activity, a biomarker of active disease, a positive correlation between serum IL-17F and alanine transaminase (rs: 0.4739; P = 0.0009) and aspartate transaminase (rs: 0.4984; P = 0.0004) levels was found. A cytokine signature profile associated with type 2 AIH was characterized by high serum IL-21 (type 1 AIH: 0.66 pg/mL; type 2 AIH: 331.1 pg/mL; P = 0.0042) and IL-22 (type 1 AIH: 0.1 pg/mL; type 2 AIH: 55.26 pg/mL; P = 0.0028) levels.
  
  
  CONCLUSIONS
  We show for the first time, differential regulation of certain pro-inflammatory cytokines associated with disease progression and AIH type in Mexican patients.
authors.affiliation: Laboratorio Multidisciplinario en Ciencias Biomédicas, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México; Doctorado en Ciencias Biomédicas, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Veracruz, México.
authors.forename: Pablo
authors.initials: P
authors.lastname: Thomas-Dupont
authors.affiliation: Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México.
authors.forename: José M
authors.initials: JM
authors.lastname: Remes-Troche
authors.affiliation: Laboratorio Multidisciplinario en Ciencias Biomédicas, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México; Doctorado en Ciencias Biomédicas, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Veracruz, México.
authors.forename: Irma Y
authors.initials: IY
authors.lastname: Izaguirre-Hernández
authors.affiliation: Laboratorio Multidisciplinario en Ciencias Biomédicas, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México; Doctorado en Ciencias Biomédicas, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Veracruz, México.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Sánchez-Vargas
authors.affiliation: Laboratorio Multidisciplinario en Ciencias Biomédicas, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México; Doctorado en Ciencias Biomédicas, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Veracruz, México.
authors.forename: Mathywz de J
authors.initials: Mde J
authors.lastname: Maldonado-Rentería
authors.affiliation: Laboratorio Multidisciplinario en Ciencias Biomédicas, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México; Doctorado en Ciencias Biomédicas, Centro de Investigaciones Biomédicas, Universidad Veracruzana, Xalapa, Veracruz, México.
authors.forename: Karina G
authors.initials: KG
authors.lastname: Hernández-Flores
authors.affiliation: Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México D.F.
authors.forename: Aldo
authors.initials: A
authors.lastname: Torre
authors.affiliation: Centro Estatal de la Transfusión Sanguínea (CETS), Boca del Río, Veracruz, México.
authors.forename: Elidé
authors.initials: E
authors.lastname: Bravo-Sarmiento
authors.affiliation: Laboratorio Multidisciplinario en Ciencias Biomédicas, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México.
authors.forename: Héctor
authors.initials: H
authors.lastname: Vivanco-Cid
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000974:Antibodies, Antinuclear / Q000276:immunology; D001219:Aspartate Aminotransferases / Q000097:blood; D001323:Autoantibodies / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D019693:Hepatitis, Autoimmune / Q000145:classification / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008800:Mexico; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult; D000097043:Interleukin-22; D000098546:Interleukin-21
chemical_list: D000410:Alanine Transaminase; D000974:Antibodies, Antinuclear; D001219:Aspartate Aminotransferases; D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D016753:Interleukin-10; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D000097043:Interleukin-22; D000098546:Interleukin-21; C508609:IL10 protein, human; C508717:IL17A protein, human; C440021:IL17F protein, human; C508600:IL6 protein, human; C439524:TNF protein, human; C060729:anti-liver kidney microsome antibody; C051931:myasthenia gravis anti-skeletal muscle antibody