血清颗粒蛋白前体在Ⅰ型自身免疫性肝炎预后评估中的价值

doi:10.3969/j.issn.1673-8640.2023.03.008

检验医学 ›› 2023, Vol. 38 ›› Issue (3): 245-250.DOI: 10.3969/j.issn.1673-8640.2023.03.008

血清颗粒蛋白前体在Ⅰ型自身免疫性肝炎预后评估中的价值

任荟蓉¹, 徐婷娟², 武涛¹, 黄玫³, 杨亮⁴

1.中国科学技术大学附属第一医院检验科，安徽合肥 230001
2.中国科学技术大学附属第一医院老年病研究所，安徽合肥 230001
3.中国科学技术大学附属第一医院普外科实验室，安徽合肥230001
4.中国科学技术大学附属第一医院感染性疾病科，安徽合肥 230001

收稿日期:2021-07-26 修回日期:2022-06-14 出版日期:2023-03-28 发布日期:2023-05-24
作者简介:任荟蓉，女，1990年生，学士，检验师，主要从事临床免疫学检验工作。
基金资助:
安徽省自然科学基金面上项目(2008085MH253)

Role of serum progranulin in type Ⅰ autoimmune hepatitis prognosis evaluation

REN Huirong¹, XU Tingjuan², WU Tao¹, HUANG Mei³, YANG Liang⁴

1. Department of Clinical Laboratory，the First Affiliated Hospital of the University of Science and Technology of China，Hefei 230001，Anhui，China
2. Geriatrics Institute，the First Affiliated Hospital of the University of Science and Technology of China，Hefei 230001，Anhui，China
3. General Surgery Laboratory，the First Affiliated Hospital of the University of Science and Technology of China，Hefei 230001，Anhui，China
4. Department of Infectious Diseases，the First Affiliated Hospital of the University of Science and Technology of China，Hefei 230001，Anhui，China

Received:2021-07-26 Revised:2022-06-14 Online:2023-03-28 Published:2023-05-24

摘要/Abstract

摘要： 目的探讨血清颗粒蛋白前体（PGRN）在Ⅰ型自身免疫性肝炎（AIH）预后评估中的价值。方法选取活动期Ⅰ型AIH患者39例（AIH组）、健康体检者35名（正常对照组）。收集所有研究对象的一般资料和实验室指标[白细胞（WBC）计数、血清肝脏酶类、免疫球蛋白和自身抗体]检测结果，并检测血清PGRN、白细胞介素（IL）-17和IL-10水平。分析Ⅰ型AIH患者治疗前、后各项指标的差异和复发患者血清PGRN的变化。采用Spearman相关分析评估各项指标之间的相关性。采用受试者工作特征（ROC）曲线评价血清PGRN判断Ⅰ型AIH患者复发的效能。结果 AIH组血清PGRN、IL-17水平显著高于正常对照组（P<0.05），血清IL-10水平显著低于正常对照组（P<0.05）。Ⅰ型AIH患者PGRN与IL-17、γ-谷氨酰基转移酶（GGT）、IgG和IgM均呈正相关性（r值分别为0.410、0.489、0.596、0.525，P<0.05）。Ⅰ型AIH患者治疗后血清PGRN水平均显著低于治疗前（P<0.01）。复发组血清PGRN水平显著高于未复发组（P<0.05）。ROC曲线分析结果显示，血清PGRN判断Ⅰ型AIH患者复发的曲线下面积（AUC）为0.78，以80.75 pg/mL为最佳临界值，敏感性为62.50%，特异性为83.33%。结论 Ⅰ型AIH患者血清PGRN水平升高，且与AIH的疗效和复发有关，或可作为评价肝脏炎症损伤程度和疾病复发的指标之一。

关键词: 颗粒蛋白前体, 白细胞介素17, 白细胞介素10, 自身免疫性肝炎

Abstract: Objective To investigate the expression of serum progranulin（PGRN） in the prognosis evaluation of patients with type Ⅰ autoimmune hepatitis（AIH）. Methods Totally，39 active type Ⅰ AIH patients were enrolled as AIH group，and 35 healthy subjects were enrolled as control group. The general data and the determination results of white blood cell（WBC） count，serum liver enzymes，immunoglobulins and autoantibodies were collected. Serum levels of PGRN，interleukin（IL）-17 and IL-10 were determined. The changes in serum PGRN before and after treatment and its correlation with recurrence were analyzed. Spearman correlation analysis was used to analyze the correlations of serum PGRN with IL-17，IL-10 and clinical parameters. Receiver operating characteristic （ROC） curve was used to evaluate the efficiency of serum PGRN in the diagnosis of type Ⅰ AIH recurrence. Results Compared with healthy control group，serum PGRN and IL-17 were increased in AIH group（P<0.05），while IL-10 was decreased（P<0.05）. Serum PGRN was positively correlated with IL-17，gamma-glutamyltransferase（GGT），immunoglobulin G（IgG） and immunoglobulin M（IgM）（r values were 0.410，0.489，0.596 and 0.525，P<0.05）. Serum PGRN level in AIH group after treatment was lower than that before treatment（P<0.01）. Serum PGRN was higher in recurrence patients than that in non-recurrence patients（P<0.05）. ROC curve results showed that the area under curve of serum PGRN was 0.78 for predicting type Ⅰ AIH recurrence. When the optimal cut-off value was 80.75 pg/mL，the sensitivity was 62.50%，and the specificity was 83.33%. Conclusions Serum PGRN is increased in type Ⅰ AIH patients，it is related to AIH treatment efficiency and recurrence，and it can be used as an indicator to evaluate liver inflammation，injury severity and recurrence.

Key words: Progranulin, Interleukin 17, Interleukin 10, Autoimmune hepatitis

中图分类号:

R446.1

任荟蓉, 徐婷娟, 武涛, 黄玫, 杨亮. 血清颗粒蛋白前体在Ⅰ型自身免疫性肝炎预后评估中的价值[J]. 检验医学, 2023, 38(3): 245-250.

REN Huirong, XU Tingjuan, WU Tao, HUANG Mei, YANG Liang. Role of serum progranulin in type Ⅰ autoimmune hepatitis prognosis evaluation[J]. Laboratory Medicine, 2023, 38(3): 245-250.

图/表 6

参考文献 24

[1]	TANAKA A. Autoimmune hepatitis:2019 update[J]. Gut Liver, 2020, 14(4):430-438. DOI URL
[2]	KOMORI A. Recent updates on the management of autoimmune hepatitis[J]. Clin Mol Hepatol, 2021, 27(1):58-69. DOI PMID
[3]	UYANIK M, SERTOGLU E, KAYADIBI H. Early diagnosis of autoimmune hepatitis on the basis of demographic and biochemical parameters[J]. Eur J Gastroenterol Hepatol, 2014, 26(9):1060-1061.
[4]	LIBERAL R, MIELI-VERGANI G, VERGANI D. Autoimmune hepatitis:from mechanisms to therapy[J]. Rev Clin Esp(Barc), 2016, 216(7):372-383.
[5]	LIANG M, LIWEN Z, YUN Z, et al. The imbalance between Foxp3+Tregs and Th1/Th17/Th22 cells in patients with newly diagnosed autoimmune hepatitis[J]. J Immunol Res, 2018, 2018:3753081.
[6]	POGONOWSKA M, PONIATOWSKI Ł A, WAWRZYNIAK A, et al. The role of progranulin(PGRN) in the modulation of anti-inflammatory response in asthma[J]. Cent Eur J Immunol, 2019, 44(1):97-101.
[7]	JING C, ZHANG X, SONG Z, et al. Progranulin mediates proinflammatory responses in systemic lupus erythematosus:implications for the pathogenesis of systemic lupus erythematosus[J]. J Interferon Cytokine Res, 2020, 40(1):33-42. DOI URL
[8]	ALVAREZ F, BERG P A, BIANCHI F B, et al. International autoimmune hepatitis group report:review of criteria for diagnosis of autoimmune hepatitis[J]. J Hepatol, 1999, 31(5):929-938. DOI URL
[9]	TIAN G, JIN X, WANG Q, et al. Recent advances in the study of progranulin and its role in sepsis[J]. Int Immunopharmacol, 2020, 79:106090. DOI URL
[10]	WEI J, HETTINGHOUSE A, LIU C. The role of progranulin in arthritis[J]. Ann N Y Acad Sci, 2016, 1383(1):5-20. DOI URL
[11]	JIAN J, KONOPKA J, LIU C. Insights into the role of progranulin in immunity,infection,and inflammation[J]. J Leukoc Biol, 2013, 93(2):199-208. DOI URL
[12]	ARECHAVALETA-VELASCO F, PEREZ-JUAREZ C E, GERTON G L, et al. Progranulin and its biological effects in cancer[J]. Med Oncol, 2017, 34(12):194. DOI URL
[13]	WANG S, WEI J, FAN Y, et al. Progranulin is positively associated with intervertebral disc degeneration by interaction with IL-10 and IL-17 through TNF pathways[J]. Inflammation, 2018, 41(5):1852-1863. DOI PMID
[14]	LI L, LI L, XIAO L, et al. Progranulin ameliorates coxsackievirus-B3-induced viral myocarditis by downregulating Th1 and Th17 cells[J]. Exp Cell Res, 2018, 367(2):241-250. DOI PMID
[15]	WEI F, ZHANG Y, JIAN J, et al. PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner[J]. Sci Rep, 2014, 4:7023. DOI PMID
[16]	ZHAO Y P, TIAN Q Y, LIU C J. Progranulin deficiency exaggerates,whereas progranulin-derived Atsttrin attenuates,severity of dermatitis in mice[J]. FEBS Lett, 2013, 587(12):1805-1810. DOI URL
[17]	WEI F, ZHANG Y, JIAN J, et al. PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner[J]. Sci Rep, 2014, 4:7023. DOI PMID
[18]	WEI F, ZHANG Y, ZHAO W, et al. Progranulin facilitates conversion and function of regulatory T cells under inflammatory conditions[J]. PLoS One, 2014, 9(11):e112110. DOI URL
[19]	ZHAO Y P, LIU B, TIAN Q Y, et al. Progranulin protects against osteoarthritis through interacting with TNF-α and β-catenin signalling[J]. Ann Rheum Dis, 2015, 74(12):2244-2253. DOI URL
[20]	MATSUBARA T, MITA A, MINAMI K, et al. PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue[J]. Cell Metab, 2012, 15(1):38-50. DOI PMID
[21]	TANAKA A, TSUKAMOTO H, MITOMA H, et al. Serum progranulin levels are elevated in patients with systemic lupus erythematosus,reflecting disease activity[J]. Arthritis Res Ther, 2012, 14(6):R244. DOI URL
[22]	MONTANO-LOZA A J, CARPENTER H A, CZAJA A J. Consequences of treatment withdrawal in type 1 autoimmune hepatitis[J]. Liver Int, 2007, 27(4):507-515. DOI URL
[23]	CZAJA A J, MENON K V, CARPENTER H A. Sustained remission after corticosteroid therapy for type 1 autoimmune hepatitis:a retrospective analysis[J]. Hepatology, 2002, 35(4):890-897. DOI URL
[24]	JIAN J, LI G, HETTINGHOUSE A, et al. Progranulin:a key player in autoimmune diseases[J]. Cytokine, 2018, 101:48-55. DOI URL

组别	例数	WBC计数/（×10⁹/L）	ALT/（U/L）	AST/（U/L）	GGT/（U/L）	ALP/（U/L）
AIH组	39	7.51±3.83	142.5±101.2	137.3±58.1	189.2±63.7	175.3±39.2
正常对照组	35	5.13±3.80	22.8±7.9	21.9±6.1	25.4±6.8	91.3±24.2
统计值		2.314	17.898	16.562	20.365	6.237
P值		0.035	0.000	0.000	0.000	0.000

组别	例数	WBC计数/（×10⁹/L）	ALT/（U/L）	AST/（U/L）	GGT/（U/L）	ALP/（U/L）
AIH组	39	7.51±3.83	142.5±101.2	137.3±58.1	189.2±63.7	175.3±39.2
正常对照组	35	5.13±3.80	22.8±7.9	21.9±6.1	25.4±6.8	91.3±24.2
统计值		2.314	17.898	16.562	20.365	6.237
P值		0.035	0.000	0.000	0.000	0.000

组别	例数	PGRN/（ng/mL）	IL-10/（pg/mL）	IL-17/（pg/mL）
AIH组	39	72.35±12.92	5.37±2.80	13.52±6.78
正常对照组	35	33.04±9.26	17.21±6.99	2.89±0.54
t值		9.61	13.28	13.77
P值		0.000	0.000	0.000

组别	例数	PGRN/（ng/mL）	IL-10/（pg/mL）	IL-17/（pg/mL）
AIH组	39	72.35±12.92	5.37±2.80	13.52±6.78
正常对照组	35	33.04±9.26	17.21±6.99	2.89±0.54
t值		9.61	13.28	13.77
P值		0.000	0.000	0.000

组别	例数	PGRN/（ng/mL）	WBC计数/（×10⁹/L）	ALT/（U/L）	AST/（U/L）	GGT/（U/L）
治疗前	12	75.88±12.34	7.71±4.35	159.6±125.7	135.7±52.9	192.3±58.7
治疗后	12	52.47±15.43	5.68±2.96	37.2±10.8	46.1±12.3	74.3±23.8
t值		4.702	2.825	15.081	10.242	11.351
P值		0.000 6	0.008 0	0.000 0	0.000 0	0.000 0
组别	ALP/（U/L）	TB/（μmol/L）	DBil/（μmol/L）	IgG/（g/L）	IgM/（g/L）	IgA/（g/L）
治疗前	179.4±31.8	97.5±26.8	71.4±22.6	19.9±5.2	7.9±1.9	4.5±2.7
治疗后	94.1±25.8	24.3±8.1	18.4±8.9	8.6±3.7	4.3±2.1	2.8±1.5
t值	7.109	12.450	10.258	7.159	2.928	3.952
P值	0.000 0	0.000 0	0.000 0	0.000 0	0.007 0	0.000 0

血清颗粒蛋白前体在Ⅰ型自身免疫性肝炎预后评估中的价值

Role of serum progranulin in type Ⅰ autoimmune hepatitis prognosis evaluation

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 24

相关文章 15

编辑推荐

Metrics

[1]	贺龙, 王莎, 程利萍, 廖子蔚, 王东红. 血清AChE、IL-17与单纯疱疹病毒性脑炎患者认知功能障碍的相关性[J]. 检验医学, 2023, 38(8): 719-724.
[2]	丁肖媛, 戴劲盛, 焦荣红, 马素丽, 朱海峰, 吴梦雅, 车艳然, 张蕾. 肥胖/超重对哮喘发作期患儿Th1/Th2和Th17/Treg细胞因子的影响[J]. 检验医学, 2023, 38(8): 748-752.
[3]	周莹, 任益慧, 李广明. AIH患儿血清miR-148a表达及其与炎症因子的相关性[J]. 检验医学, 2023, 38(12): 1130-1134.
[4]	杨艳敏, 彭梦乐, 连文萍. 直肠癌患者MDSC百分比和RORα mRNA、IL-17E mRNA、FOXP3 mRNA表达的临床意义[J]. 检验医学, 2023, 38(1): 23-27.
[5]	程惠芬. 血清P-选择素、ICAM-1、IL-17A水平在HBV感染相关疾病中的临床价值[J]. 检验医学, 2021, 36(6): 646-649.
[6]	陈朴, 马艳婷, 陈楠, 于正麟, 程韵枫, 潘柏申, 郭玮, 王蓓丽. 炎症相关细胞因子与Ph阴性骨髓增殖性肿瘤的相关性[J]. 检验医学, 2021, 36(2): 167-172.
[7]	柯文才, 顾芸霞, 刘洁, 金小玲. 桥本甲状腺炎患者血清IL-17、IL-35与维生素D的相关性[J]. 检验医学, 2021, 36(2): 181-184.
[8]	洪伟祥, 宋云霄, 贾玖德, 张文通, 沈文晖, 黄晋旺, 张雷, 米尔萨力江·亚森, 张银网. 术前血清IL-2R、IL-6和IL-8水平与老年髋关节骨折术后30 d预后的相关性[J]. 检验医学, 2021, 36(11): 1159-1163.
[9]	姜文佳. 骨关节炎患者血清1, 25（OH） ₂D₃、IL-17和IL-10水平的变化及临床意义[J]. 检验医学, 2019, 34(3): 202-205.
[10]	陆光辉, 褚志华, 周发为, 杨年安, 杨洁, 王姣平, 曾守逵. IL-17、IL-22和IL-10在支气管哮喘患儿外周血单个核细胞中的表达及意义[J]. 检验医学, 2019, 34(1): 28-32.
[11]	王晶, 陈丽, 刘春华, 李丽春. 血清IL-17A水平在多囊卵巢综合征患者中的临床意义[J]. 检验医学, 2018, 33(7): 601-603.
[12]	阎淑, 张泓. Del-1对特异性过敏患儿嗜酸性粒细胞表面ICAM-1表达的影响[J]. 检验医学, 2018, 33(1): 67-71.
[13]	周韵娇，张丽红，李鹏，叶鲜妩，牛建英. IL-17和IL-23在成人原发性肾病综合征患者中的变化及意义[J]. 检验医学, 2015, 30(6): 554-558.
[14]	张国英, 钮晓红, 徐卫平, 夏厦. 淋巴结核患者外周血CD4⁺CD25^highFoxP3⁺调节性T淋巴细胞以及血浆IFN-γ和IL-10水平及其临床意义[J]. 检验医学, 2015, 30(1): 31-35.
[15]	丁庆莉, 唐古生, 贺铮雯, 沈茜, 秦阳华. 慢性乙型肝炎患者外周血Th17细胞比例和IL-17表达水平的临床意义[J]. 检验医学, 2014, 29(1): 15-20.