自身免疫性肝病患者外周血CD34+细胞和血清白细胞介素-3水平变化及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2025.01.017

摘要/Abstract

摘要： 目的探讨自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)和AIH-PBC重叠综合征(AIH-PBC OS)患者外周血白细胞分化抗原34(CD34)阳性细胞和血清白细胞介素-3(IL-3)水平变化及其临床意义。方法 2019年6月～2022年12月我院诊治的AIH患者40例、PBC患者35例和AIH-PBC OS患者25例,分别给予泼尼松龙、熊去氧胆酸或两者联合治疗,观察1年。使用流式细胞仪检测外周血CD34⁺细胞百分比,采用ELISA法检测血清IL-3水平,使用全自动生化分析仪检测血生化指标,采用免疫印迹法检测血清抗gp210抗体、抗sp100 抗体、抗线粒体M2抗体(AMA-M2)、抗肝肾微粒体I型抗体(LKM-I)、抗核抗体(ANA)和抗平滑肌抗体(ASMA)。结果治疗前,AIH组血清ALT和AST水平分别为(136.8±9.8)U/l和(116.3±28.1)U/l,在治疗12个月末,分别降至(36.8±4.8)U/l和(46.3±8.1)U/l,差异显著(P<0.05);治疗前,PBC组血清TBIL、ALP和GGT水平分别为(51.4±5.7)μmol/l、(321.1±30.0)U/l和(471.5±58.8)U/l,治疗后分别降至(31.2±4.6)μmol/l、(224.8±29.0)U/l和(271.7±48.9)U/l,差异显著(P<0.05);治疗前,AIH-PBC OS组血清TBIL、ALT、AST、ALP和GGT水平分别为(28.3±5.7)μmol/l、(90.6±12.3)U/l、(89.6±11.9)U/l、(252.3±23.6)U/l和(323.6±46.3)U/l,治疗后分别降低至(20.4±4.6)μmol/l、(50.7±11.4)U/l、(39.4±10.1)U/l、(157.6±21.4)U/l和(228.8±41.8)U/l,差异显著(P<0.05);治疗前,AIH、PBC和AIH-PBC OS组外周血CD34⁺细胞百分比分别为(8.8±2.1)%、(10.2±2.4)%和(12.6±3.2)%,治疗后分别降低至(4.7±1.2)%、(5.1±1.3)%和(5.0±1.2)%,差异显著(P<0.05),血清IL-3水平分别为(46.3±7.8)pg/ml、(50.7±8.4)pg/ml和(58.2±9.7)pg/ml,治疗后分别降低至(32.7±5.4)pg/ml、(33.5±5.6)pg/ml和(30.9±5.2)pg/ml,差异显著(P<0.05)。结论 AIH、PBC和AIH-PBC OS患者血清CD34和IL-3水平升高,是否可通过监测它们水平变化以评估病情还需要继续观察。

关键词: 自身免疫性肝炎, 原发性胆汁性肝硬化, 白细胞分化抗原34, 白细胞介素-3

Abstract: Objective The aim of this study was to investigate clinical implications of peripheral blood leukocyte differentiation antigen 34 (CD34) positive mononuclear cell and interleukin-3 (IL-3) level changes in patients with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and AIH-PBC overlap syndrome (AIH-PBC OS). Methods 40 patients with AIH, 35 patients with PBC and 25 patients with AIH-PBC OS were admitted to our hospital between June 2019 and December 2022, and they received prednisolone, ursodeoxycholic acid (UDCA) or combination of them therapy for 12 months. Percentage of peripheral blood CD34⁺ cells was detected by FCM, serum IL-3 level was measured by ELISA, and serum anti-gp210 antibody, anti-SP100 antibody, anti-mitochondrial M2 antibody (AMA-M2), anti-liver and kidney microsomal type I antibody (LKM-I) were detected by Western blot. Results At presentation, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in patients with AIH were (136.8±9.8)U/l and (116.3±28.1)U/l, while by end of 12 month treatment, they returned to (36.8±4.8)U/l and (46.3±8.1)U/l, respectively (P<0.05); serum total bilirubin (TBIL), alkaline phosphatase (ALP) and glutamyl transferase (GGT) levels in patients with PBC were (51.4±5.7)μmol/l, (321.1±30.0)U/l and (471.5±58.8)U/l, and they decreased to (31.2±4.6)μmol/l, (224.8±29.0)U/l and (271.7±48.9)U/l, respectively by end of 12-month treatment (P<0.05); serum TBIL, ALT, AST, ALP and GGT levels in patients with AIH-PBC OS were (28.3±5.7)μmol/l, (90.6±12.3)U/l, (89.6±11.9)U/l, (252.3±23.6)U/l and (323.6±46.3)U/l, and they all decreased to (20.4±4.6)μmol/l, (50.7±11.4)U/l, (39.4±10.1)U/l, (157.6±21.4)U/l and (228.8±41.8)U/l, respectively by end of 12-month treatment (P<0.05); percentages of peripheral blood CD34⁺ cells in patients with AIH, PBC and AIH-PBC OS were (8.8±2.1)%, (10.2±2.4)% and (12.6±3.2)%, and they decreased to (4.7±1.2)%, (5.1±1.3)% and (5.0±1.2)%(all P<0.05), and serum IL-3 levels were (46.3±7.8)pg/ml, (50.7±8.4)pg/ml and (58.2±9.7)pg/ml, and they all decreased to (32.7±5.4)pg/ml, (33.5±5.6)pg/ml and (30.9±5.2)pg/ml, respectively, by end of 12-month treatment (P<0.05). Conclusion Serum CD34 and IL-3 levels in patients with AIH, PBC and AIH-PBC OS increase, which might be surveillance parameters for assessment of the entity.

Key words: Autoimmune hepatitis, Primary biliary cirrhosis, Leukocyte differentiation antigen 34, Interleukin-3

王宝林, 杜潘艳, 李小超, 侯斌. 自身免疫性肝病患者外周血CD34⁺细胞和血清白细胞介素-3水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2025, 28(1): 64-67.

Wang Baolin, Du Panyan, Li Xiaochao, et al. Peripheral blood CD34⁺ cell and serum interleukin-3 level changes in patients with autoimmune liver diseases[J]. Journal of Practical Hepatology, 2025, 28(1): 64-67.

参考文献

[1] Colapietro F, Maisonneuve P, Lytvyak E, et al. Incidence and predictors of hepatocellular carcinoma in patients with autoimmune hepatitis. J Hepatol, 2024, 80(1):53-61.
[2] 黄静, 商惠民, 王菁, 等. 不同肝组织炎症分级和纤维化分期的自身免疫性肝炎患者外周血单个核细胞TLR2和CTLA-4水平变化研究. 实用肝脏病志, 2023,26(5):658-661.
[3] Díaz-González Á, Hernández-Guerra M, Pérez-Medrano I, et al. Budesonide as first-line treatment in patients with autoimmune hepatitis seems inferior to standard predniso(lo)ne administration. Hepatology, 2023, 77(4):1095-1105.
[4] Hirschfield GM, Shiffman ML, Gulamhusein A, et al. Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study. Hepatology, 2023, 78(2):397-415.
[5] Acharya S, Shrestha S, Poddar E, et al. Antimitochondrial antibody-negative primary biliary cirrhosis with secondary Sjogren syndrome: a case report. Ann Med Surg (Lond), 2023, 85(11):5645-5648.
[6] Surdea-Blaga T, Cărăgu RL, Caraiani C, et al. Overlap syndrome of autoimmune hepatitis and primary biliary cholangitis complicated with atypical hepatocellular carcinoma: a case report. J Med Case Rep, 2023, 17(1):328.
[7] 居峰, 姚上志, 王栋, 等. 自身免疫性肝炎患者血清白细胞分化抗原38和白细胞介素21水平变化及其临床意义探讨. 实用肝脏病杂志, 2022, 25(6):824-827.
[8] Rani L, Kumar A, Karhade J, et al. IL-3 regulates the differentiation of pathogenic Th17 cells. Eur J Immunol, 2022, 52(11):1842-1858.
[9] 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年). 中华肝脏病杂志, 2022, 30(5):482-492.
[10] 中华医学会肝病学分会. 原发性胆汁性胆管炎的诊断和治疗指南(2021年). 中华肝脏病杂志, 2022, 30(3):264-275.
[11] Kok B, Abraldes JG. Child-Pughclassification: Time to abandon? Semin Liver Dis, 2019, 39(1):96-103.
[12] Carbone M, Sharp SJ, Flack S, et al. The UK-PBC risk scores: Derivation and validation of a scoring system for long-term prediction of end-stage liver disease in primary biliary cholangitis. Hepatology, 2016, 63(3):930-950.
[13] Long J, Yang SY, Huang MX, et al. Spontaneous development of an autoimmune hepatitis - primary biliary cholangitis overlap syndrome in dnTGFβRII Aire-/- mice. J Pathol, 2023, 260(2):222-234.
[14] Hussain N, Trivedi PJ. The inconvenient truth of primary biliary cholangitis/autoimmune hepatitis overlap syndrome. Clin Liver Dis, 2022, 26(4):657-680.
[15] 郭银燕, 岳枝, 盖晓冬, 等. 自身免疫性肝炎-原发性胆汁性胆管炎重叠综合征患者临床和肝组织病理学特征分析. 实用肝脏病杂志, 2023, 26(3):372-375.
[16] Subramanian S, Thoms JAI, Huang Y, et al. Genome-wide transcription factor-binding maps reveal cell-specific changes in the regulatory architecture of human HSPCs. Blood, 2023, 142(17):1448-1462.
[17] Du L, Sun X, Gong H, et al. Single cell and lineage tracing studies reveal the impact of CD34⁺ cells on myocardial fibrosis during heart failure. Stem Cell Res Ther, 2023, 14(1):33.
[18] Tampakis A, Weixler B, Rast S, et al. Nestin and CD34 expression in colorectal cancer predicts improved overall survival. Acta Oncol, 2021, 60(6):727-734.
[19] Coppin E, Zhang X, Ohayon L, et al. Peripheral ischemia imprints epigenetic changes in hematopoietic stem cells to propagate inflammation and atherosclerosis.Arterioscler Thromb Vasc Biol, 2023, 43(6):889-906.
[20] Hicks NJ, Crozier RWE, MacNeil AJ. JNK signaling during IL-3-mediated differentiation contributes to the c-kit-potentiated allergic inflammatory capacity of mast cells. J Leukoc Biol, 2023, 114(1):92-105.
[21] Kiss MG, Mindur JE, Yates AG, et al. Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis. Immunity, 2023, 56(7):1502-1514,e8.
[22] Yue R, Liu X. Impact of transarterial chemoembolization or hepatic artery infusion chemotherapy on liver function after hepatocellular carcinoma resection: an observational study. Digestion, 2023, 104(4):291-298.
[23] Xiao F, Qiu XF, You CW, et al. Influence of liver function after laparoscopy-assisted vs totally laparoscopic gastrectomy. World J Gastrointest Surg, 2023, 15(5):859-870.
[24] Sultana I, Sultana N, Rabbany MA, et al. Evaluation of liver function tests in β-Thalassemia major children. Mymensingh Med J, 2022, 31(4):894-899.