Thomas-Dupont Pablo, Remes-Troche José M, Izaguirre-Hernández Irma Y, Sánchez-Vargas Luis A, Maldonado-Rentería Mathywz de J, Hernández-Flores Karina G, Torre Aldo, Bravo-Sarmiento Elidé, Vivanco-Cid Héctor
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.
Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Médico-Biológicas, Universidad Veracruzana, Veracruz, México.
Ann Hepatol. 2016 Jul-Aug;15(4):550-8.
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.
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.
We show for the first time, differential regulation of certain pro-inflammatory cytokines associated with disease progression and AIH type in Mexican patients.
背景与目的。自身免疫性肝炎（AIH）是一种肝脏慢性炎症性疾病，其组织破坏和/或修复所涉及的免疫机制仍不清楚。已表明不同的促炎细胞因子在AIH发病机制中起决定性作用。在此，我们旨在比较2型AIH患者与1型AIH患者及健康对照（HC）中促炎和抗炎细胞因子如IL-6、TNF-α、IL-17A/F、IL-21、IL-22、IL-23和IL-10的循环水平。我们的研究招募了46名墨西哥AIH患者。根据免疫血清学标志物将患者分为1型或2型AIH。纳入44名健康个体的血清样本作为对照。采用ELISA技术测定血清细胞因子水平。
与健康对照相比，AIH患者血清中IL-17F、IL-21、IL-23、IL-10、IL-6和TNF-α水平显著升高，但IL-17A和IL-22水平未升高。当根据转氨酶活性（一种活动性疾病的生物标志物）对患者进行分组时，发现血清IL-17F与丙氨酸转氨酶（rs：0.4739；P = 0.0009）和天冬氨酸转氨酶（rs：0.4984；P = 0.0004）水平呈正相关。与2型AIH相关的细胞因子特征性谱表现为血清IL-21（1型AIH：0.66 pg/mL；2型AIH：331.1 pg/mL；P = 0.0042）和IL-22（1型AIH：0.1 pg/mL；2型AIH：55.26 pg/mL；P = 0.0028）水平较高。
我们首次表明墨西哥患者中某些促炎细胞因子与疾病进展和AIH类型存在差异调节。
