自身免疫性肝炎患者血清瘦素、外周血调节性T细胞和Th17细胞水平变化*

doi:10.3969/j.issn.1672-5069.2024.05.017

摘要/Abstract

摘要： 目的探讨自身免疫性肝炎(AIH)患者血清瘦素水平及外周血调节性T细胞(Tregs)和辅助性T细胞17(Th17)比例变化及其临床意义。方法 2018年3月～2023年3月我院诊治的AIH患者69例,均接受肝穿刺活检和泼尼松和硫唑嘌呤联合治疗。采用ELISA法检测血清细胞因子水平,使用流式细胞仪检测外周血Tregs和Th17淋巴细胞百分比,并计算Th17/Tregs细胞比值。结果 22例重症AIH血清血清瘦素、IL-17、IL-22和TNF-α水平、外周血Th17/CD4⁺细胞百分比和Th17/Tregs比值分别为(335.6±84.2)ng/mL、(18.5±4.1)pg/mL、(48.7±11.4)pg/mL、(5.6±0.9)ng/mL、(3.3±1.2)%和(20.1±3.0),显著高于47例轻中症组【分别为(66.9±13.8)ng/mL、(6.9±2.5)pg/mL、(13.8±3.3)pg/mL、(1.1±0.4)ng/mL、(2.5±0.3)%和(12.4±1.5),P<0.05】,而外周血血小板计数、血清IL-10水平和外周血Tregs/CD4⁺细胞百分比分别为(129.8±29.4)×10⁹/L、(2.3±0.7)pg/mL和(1.6±0.4)%,显著低于轻中症患者【分别为(174.2±35.6)×10⁹/L、(4.8±0.9)pg/mL和(2.0±0.8)%,P<0.05】;经肝组织学检查,发现肝组织炎症G1～2级42例和G3～4级27例;G3～4级AIH组血清瘦素、IL-17、IL-22和TNF-α水平和外周血Th17/CD4⁺百分比和Th17/Tregs细胞比值显著高于G1～2级,而血小板计数、Tregs/CD4⁺细胞百分比和血清IL-10水平显著低于G1～2级组(P<0.05);所有患者经治疗均获得完全应答,其中<3个月、3～6个月和>6个月应答的AIH患者分别为35例、23例和11例;血清瘦素及外周血Tregs/CD4⁺和Th17/CD4⁺细胞百分比或Th17/Tregs细胞比值高的患者应答时间显著减慢(P＜0.05)。结论监测AIH患者血清瘦素及外周血调节性T细胞和Th17细胞百分比可能有助于预测免疫抑制治疗的疗效,值得临床进一步深入研究。

关键词: 自身免疫性肝炎, 泼尼松, 瘦素, 调节性T细胞, 辅助性T细胞, 治疗

Abstract: Objective This study was conducted to explore the clinical implications of serum leptin level, and peripheral blood regulatory T cells (Tregs) and helper T 17 (Th17) cells in patients with autoimmune hepatitis (AIH). Methods 69 patients with AIH were enrolled in our hospital between March 2018 and March 2023, and all underwent liver biopsies and received standardized prednisone and azathioprine combination therapy. Serum cytokine levels were assayed by ELISA, and the percentages of peripheral blood Tregs and Th17 cells were detected by FCM. Results Serum leptin, IL-17, IL-22 and TNF-α, and percentage of blood Th17/CD4⁺ cells and the Th17/Tregs cell ratio in 22 patients with severe AIH were (335.6±84.2)ng/mL, (18.5±4.1)pg/mL, (48.7±11.4)pg/mL, (5.6±0.9)ng/mL, (3.3±1.2)% and (20.1±3.0), all significantly higher than [(66.9±13.8)ng/mL,(6.9±2.5)pg/mL, (13.8±3.3)pg/mL, (1.1±0.4)ng/mL, (2.5±0.3)% and (12.4±1.5), respectively, P<0.05], while blood platelet count, serum IL-10 level and percentage of blood Tregs/CD4⁺ cells were (129.8±29.4)×10⁹/L, (2.3±0.7)pg/mL and (1.6±0.4)%, all much lower than [(174.2±35.6)×10⁹/L, (4.8±0.9)pg/mL and (2.0±0.8)%, P<0.05]in 47 patients with mild/moderate AIH; the histo-pathological examination showed G1-2 histological activity in 42 cases and G3-4 in 27 cases; serum leptin, IL-17, IL-22 and TNF-α levels, percentage of blood Th17/CD4⁺ cell and the Th17/Tregs cell ratio in patients with G3-4 were significantly higher than, while the platelet count, percentage of Tregs/CD4⁺ cells and serum IL-10 level were much lower than in those with G1-2(P<0.05); all patients in our series obtained complete response (CR) after immunosuppression therapy, and the CR occurred less than three months in 35 cases, three to six months in 23 cases and longer than six months in 11 cases; the patients with increased serum leptin levels, percentages of blood Tregs/CD4⁺ and Th17/CD4⁺ cells, and the Th17/Tregs cell ration cost longer period for CR (P＜0.05). Conclusion The surveillance of serum leptin levels and peripheral blood Tregs and Th17 cells might predict the efficacy of immunosuppression therapy, which needs further clinical verification.

Key words: Autoimmune hepatitis, Prednisone, Leptin, Regulatory T cells, Helper T cells, Therapy

蒋叶舟, 花霞, 陈国飞, 朱青蓝, 蔡明月. 自身免疫性肝炎患者血清瘦素、外周血调节性T细胞和Th17细胞水平变化^*[J]. 实用肝脏病杂志, 2024, 27(5): 713-716.

Jiang Yezhou, Hua Xia, Chen Guofei, et al. Changes of serum leptin level and percentages of peripheral blood regulatory T cells and Th17 cells in patients with autoimmune hepatitis[J]. Journal of Practical Hepatology, 2024, 27(5): 713-716.

参考文献

[1] Komori A. Recent updates on the management of autoimmune hepatitis. Clin Mol Hepatol, 2021, 27(1):58-69.
[2] Vuerich M, Harshe R, Frank LA, et al.Altered aryl-hydrocarbon-receptor signalling affects regulatory and effector cell immunity in autoimmune hepatitis. J Hepatol, 2021, 74(1):48-57.
[3] Abend Bardagi A, Dos Santos Paschoal C, Favero GG, et al.Leptin's immune action: A review beyond satiety. Immunol Invest, 2023, 52(1):117-133.
[4] Lal D, Thakur M, Bihari C. Serum leptin serves as an inflammatory activity marker and predicts steroid response in autoimmune hepatitis. J Clin Exp Hepatol, 2020, 10(6):574-580.
[5] de Candia P, Prattichizzo F, Garavelli S, et al.The pleiotropic roles of leptin in metabolism, immunity, and cancer. J Exp Med, 2021, 218(5):e20191593.
[6] 中华医学会肝病学分会. 自身免疫性肝炎诊断和治疗指南(2021). 中华肝脏病杂志, 2022, 30(5):482-492.
[7] Onji M, Zeniya M, Yamamoto K, et al. Autoimmune hepatitis: Diagnosis and treatment guide in Japan, 2013. Hepatol Res, 2014, 44(4):368-370.
[8] Wang H, Feng X, Yan W, et al. Regulatory T cells in autoimmune hepatitis: Unveiling their roles in mouse models and patients. Front Immunol, 2020, 11:575572.
[9] Vuerich M, Wang N, Kalbasi A, et al. Dysfunctional immune regulation in autoimmune hepatitis: From pathogenesis to novel therapies. Front Immunol, 2021, 12:746436.
[10] 冯娟, 何方平. 瘦素对肝脏代谢的作用及与肝病的关系. 中国肝脏病杂志(电子版), 2022, 14(3):22-27.
[11] Petrescu AD, Grant S, Williams E, et al. Leptin enhances hepatic fibrosis and inflammation in a mouse model of cholestasis. Am J Pathol, 2022, 192(3):484-502.
[12] Marrodan M, Farez MF, Balbuena Aguirre ME, et al. Obesity and the risk of multiple sclerosis. The role of leptin. Ann Clin Transl Neurol, 2021, 8(2):406-424.
[13] Chaffey A, Hamonic G, Chand D, et al. The adjuvants polyphosphazene (PCEP) and a combination of curdlan plus leptin promote a Th17-type immune response to an intramuscular vaccine in mice.Vaccines (Basel), 2021, 9(5):507.
[14] Vollmer CM, Dias ASO, Lopes LM, et al. Leptin favors Th17/Treg cell subsets imbalance associated with allergic asthma severity. Clin Transl Allergy, 2022, 12(6):e12153.
[15] Zieba DA, Biernat W, Bar J. Roles of leptin and resistin in metabolism, reproduction, and leptin resistance. Domest Anim Endocrinol, 2020, 73:106472.
[16] Yasuda K, Takeuchi Y, Hirota K. The pathogenicity of Th17 cells in autoimmune diseases.Semin Immunopathol, 2019, 41(3):283-297.
[17] Huang Z, Li W, Su W. Tregs in autoimmune uveitis. Adv Exp Med Biol, 2021, 1278:205-227.
[18] Michalak SS, Olewicz-Gawlik A, Rupa-Matysek, et al. Autoimmune hemolytic anemia: current knowledge and perspectives.Immun Ageing, 2020, 17(1):38.
[19] Lin X, Xu A, Zhou L, et al. Imbalance of T lymphocyte subsets in adult immune thrombocytopenia. Int J Gen Med, 2021, 14:937-947.
[20] Bunte K, Beikler T. Th17 cells and the IL-23/IL-17 axis in the pathogenesis of periodontitis and immune-mediated inflammatory diseases. Int J Mol Sci, 2019, 20(14):3394.
[21] Seth P, Dubey S. IL-22 as a target for therapeutic intervention: Current knowledge on its role in various diseases. Cytokine, 2023, 169:156293.
[22] Zhou JY, Alvarez CA, Cobb BA. Integration of IL-2 and IL-4 signals coordinates divergent regulatory T cell responses and drives therapeutic efficacy. Elife, 2021, 10:e57417.
[23] Ouyang W, O'Garra A. IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation. Immunity, 2019, 50(4):871-891.

自身免疫性肝炎患者血清瘦素、外周血调节性T细胞和Th17细胞水平变化^*

Changes of serum leptin level and percentages of peripheral blood regulatory T cells and Th17 cells in patients with autoimmune hepatitis

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	韦新焕, 柳雅立, 张晶, 贾继东. 代谢相关性脂肪性肝硬化诊疗进展^*[J]. 实用肝脏病杂志, 2024, 27(5): 641-645.
[2]	张志强, 方坚, 李东良. 介入治疗肝硬化门静脉高压症研究进展与挑战^*[J]. 实用肝脏病杂志, 2024, 27(5): 650-653.
[3]	中国医药生物技术协会慢病管理分会肝病学组. 双环醇防治肝脏炎性损伤多学科专家共识[J]. 实用肝脏病杂志, 2024, 27(5): 659-668.
[4]	彭麟, 杨春, 李兴泉. 聚乙二醇干扰素α-2b联合恩替卡韦治疗HBeAg阳性慢性乙型肝炎患者疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 677-680.
[5]	冉书容, 刘洋, 雷兰. 恩替卡韦经治的慢性乙型肝炎患者发生低病毒血症危险因素及转换TAF治疗疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 681-684.
[6]	黎防, 杨宏飞, 张青. 索非布韦联合雷迪帕韦治疗慢性丙型肝炎患者疗效评价^*[J]. 实用肝脏病杂志, 2024, 27(5): 685-688.
[7]	刘雅光, 胡连智, 董一侠, 刘洋. 抗病毒治疗的基因1b型慢性丙型肝炎患者疗效及其血清γ-干扰素和白细胞介素-10水平变化^*[J]. 实用肝脏病杂志, 2024, 27(5): 689-692.
[8]	莫伟斌, 张清友, 黄晓涵, 欧阳婉爱. 达诺瑞韦联合拉维达韦治疗慢性丙型肝炎患者疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 693-696.
[9]	高怡, 沈小雪, 夏素芹, 张洁, 朱先兰. 自身免疫性肝炎和原发性胆汁性胆管炎患者血清胆汁酸成分变化及其对治疗应答的影响^*[J]. 实用肝脏病杂志, 2024, 27(5): 709-712.
[10]	朱家瑞, 葛绍锋, 叶桂云, 黄远茂. 自身免疫性肝炎患者外周血NLR和nCD64指数变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2024, 27(5): 717-720.
[11]	王燕燕, 周桐桐, 卞兆连. 原发性胆汁性胆管炎和原发性胆汁性胆管炎-自身免疫性肝炎重叠综合征患者临床与肝组织病理学特点分析^*[J]. 实用肝脏病杂志, 2024, 27(5): 721-724.
[12]	王秀娟, 朱贺, 张茹梦, 常文绘, 刘玉玉. 泼尼松联合硫唑嘌呤治疗自身免疫性肝炎患者不同减量方法的效果研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 729-732.
[13]	李瑞妮, 王莎莎, 贾泽博, 韦晓洁, 王腾. 聚桂醇和蛇毒血凝酶注射配合内镜下套扎治疗乙型肝炎肝硬化并发EVB患者疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 741-744.
[14]	田琳, 康颖, 崔洁, 石颖鹏. 内镜下套扎联合奥曲肽和凝血酶治疗肝硬化并发食管胃静脉曲张出血患者疗效研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 745-748.
[15]	李双玲, 刘丽, 陈艺, 李坤. 富马酸丙酚替诺福韦与恩替卡韦治疗高血清病毒载量的代偿期乙型肝炎肝硬化患者效果比较研究^*[J]. 实用肝脏病杂志, 2024, 27(5): 749-752.