Serum Concentrations of Th17-Associated Interleukins and Autoimmune Phenomena are Associated with the Degree of Liver Damage in Alcoholic Liver Disease

Serum Concentrations of Th17-Associated Interleukins and Autoimmune Phenomena are Associated with the Degree of Liver Damage in Alcoholic Liver Disease
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DOI:
10.15403/jgld.2014.1121.263.pak
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发表时间:
2017-09-01
影响因子:
2.1
通讯作者:
Flisiak, Robert
Flisiak, Robert
中科院分区:
医学4区
文献类型:
--
作者:
Parfieniuk-Kowerda, Anna;Swiderska, Magdalena;Flisiak, Robert

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背景和目的:最近的报告表明 Th17 反应参与酒精性肝病 (ALD) 的炎症和自身免疫反应。我们的研究旨在评估 ALD 患者血清 Th17-白细胞介素水平与肝脏特异性自身抗体的频率和肝损伤程度的关系。方法:纳入了 95 名 ALD 患者。通过ELISA评估IL-17F、IL-17A、IL-22的血清浓度。通过免疫印迹评估血清中自身抗体AMA-M2、SLA/LP、LKM-1、LC1、抗F-肌动蛋白、抗结蛋白和抗肌球蛋白的存在,通过ELISA检测ANA抗体。对结果进行肝损伤程度分析。结果:与对照组相比,ALD患者血清IL-17F显着升高(p=0.03)。血清IL-17F与MELD评分评估的肝衰竭程度存在相关性(r(s)=0.23,p=0.03)。血清 IL-22 还与 MELD 评分(r(s) =0.32,p=0.007)和 CTP 评分(r(s) =0.28,p=0.02)相关。研究组中 19% 的患者存在抗 F 肌动蛋白抗体,11% 的患者存在 ANA 抗体,对照组则没有。在患有较晚期肝病的受试者中,抗 F-肌动蛋白自身抗体的患病率较高,但在回归分析中也与 IL-17A 独立相关。此外,抗F-肌动蛋白(+)-患者的血清IL-22显着高于抗F-肌动蛋白(-)-患者(p=0.03)。结论:血清IL-17A、IL-17F、IL-22的升高与肝损伤的进展以及ALD中F-肌动蛋白的存在相关。酒精性肝病可能会引发自身免疫和自身抗体(尤其是抗 F-肌动蛋白)的形成,并可能参与 Th17 相关细胞因子的参与。
Background & Aims: Recent reports suggest an involvement of Th17 responses in inflammatory and autoimmune reactions in alcoholic liver disease (ALD). Our study aimed to assess serum levels of Th17-interleukins in ALD with regard to the frequency of liver -specific autoantibodies and degree of liver damage.Methods: Ninety-five patients with ALD were enrolled. Serum concentrations of IL-17F, IL-17A, IL-22 were assessed by ELISA. The presence of autoantibodies AMA-M2, SLA/LP, LKM-1, LC1, anti-F-actin, anti-desmin and anti-myosin in serum was assessed by immunoblotting, ANA antibodies were detected by ELISA. The results were analysed with regard to the degree of hepatic damage.Results: Serum IL-17F was significantly elevated in ALD patients compared to controls (p=0.03).There was a correlation between serum IL-17F and degree of liver failure evaluated by the MELD score (r(s) =0.23, p=0.03). Serum IL-22 also correlated with MELD score (r(s) =0.32, p=0.007) and CTP score (r(s) =0.28, p=0.02). Anti-F actin antibodies were present in 19% and ANA-antibodies in 11% of the patients in the study group, and in no subjects in the control group. The prevalence of anti-F-actin autoantibodies was higher in subjects with more advanced liver diseases but also independently associated with IL-17A in the regression analysis. Furthermore, serum IL-22 in anti-F-actin(+)-patients was significantly higher compared to anti-F-actin(-)-patients (p=0.03).Conclusions: Elevation of serum IL-17A, IL-17F, IL-22 correlated with the progression of liver damage and also with presence of F-actin in ALD. Alcoholic liver disease may trigger autoimmunity and formation of autoantibodies, especially anti-F-actin, with possible engagement of Th17-related cytokines in this process.