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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2020, Vol. 13 ›› Issue (01) : 18 -22. doi: 10.3877/cma.j.issn.1674-6902.2020.01.004

论著

KL-6和Th1/Th2细胞因子在结缔组织病相关性间质性肺炎中的表达及临床意义
岳欢欢1, 黎联2,†()   
  1. 1. 646000　泸州，西南医科大学附属医院呼吸科
    2. 646000　泸州，西南医科大学附属医院呼吸科；402260　重庆，重庆市江津区中心医院呼吸科
  • 收稿日期:2019-09-13 出版日期:2020-02-25
  • 通信作者: 黎联
  • 基金资助:
    国家自然科学基金资助项目(81200729)

Expression and clinical significance of Krebs von den Lungen-6 and T helper 1/T helper 2 cytokines in connective tissue disease-associated interstitial pneumonia

Huanhuan Yue1, Lian Li2,†()   

  1. 1. Department of Respiratory Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
    2. Department of Respiratory Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China; Department of Respiratory Medicine, Jiangjin Centre Hospital, Chongqing 402260, China
  • Received:2019-09-13 Published:2020-02-25
  • Corresponding author: Lian Li
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引用本文：

岳欢欢, 黎联. KL-6和Th1/Th2细胞因子在结缔组织病相关性间质性肺炎中的表达及临床意义[J]. 中华肺部疾病杂志(电子版), 2020, 13(01): 18-22.

Huanhuan Yue, Lian Li. Expression and clinical significance of Krebs von den Lungen-6 and T helper 1/T helper 2 cytokines in connective tissue disease-associated interstitial pneumonia[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(01): 18-22.

目的

探讨涎液化糖链抗原(KL-6)与1型辅助性T细胞/2型辅助性T细胞(Th1/Th2)细胞因子在结缔组织病相关性间质性肺炎(CTD-IP)中的表达及临床意义。

方法

选择2017.01至2019.01间收治的77例CTD-IP患者纳为CTD-IP组，60例无肺间质病变CTD者纳为CTD组，50例健康体检合格者为健康组，比较三组血清涎液化糖链抗原(KL-6)、Th1细胞因子γ干扰素(IFN-γ)、Th2细胞因子白介素-4(IL-4)及Th1/Th2(IFN-γ/IL-4)水平，并根据CTD-IP患者肺通气障碍、肺弥散功能障碍严重程度及影像学表现，对CTD-IP组患者进行分组，统计CTD-IP患者血清KL-6、IFN-γ、IL-4及IFN-γ/IL-4表达水平，并分析以上血清物质在评估CTD-IP患者病情中的效果。

结果

健康对照组、CTD组及CTD-IP组中，血清KL-6及IL-4水平呈依次上升趋势，IFN-γ及IFN-γ/IL-4水平呈依次下降趋势，组间差异均显著(P<0.05)；CTD-IP患者肺通气轻度障碍组、中度障碍组及重度障碍组中，血清KL-6及IL-4水平呈依次上升趋势，IFN-γ及IFN-γ/IL-4水平呈依次下降趋势，组间差异均显著(P<0.05)；CTD-IP患者肺弥散轻度障碍组、中度障碍组及重度障碍组中，血清KL-6及IL-4水平呈依次上升趋势，IFN-γ及IFN-γ/IL-4水平呈依次下降趋势，组间差异均显著(P<0.05)；CTD-IP患者HRCT表现活动性组血清KL-6、IFN-γ、IFN-γ/IL-4水平明显高于非活动性组(P<0.05)，IL-4水平显著低于非活动性组(P<0.05)。

结论

血清KL-6、IFN-γ、IL-6及IFN-γ/IL-6水平在反映CTD-IP患者肺通气功能障碍、肺弥散功能障碍、疾病活动期中具有良好应用价值，可作为反映CTD-IP患者病情的可靠血清参考物质。

关键词: 涎液化糖链抗原, Th1/Th2细胞因子, 间质性肺炎, 结缔组织病相关性
Objective

To investigate the expression and clinical significance of Krebs von den Lungen-6 (KL-6) and T helper 1/T helper 2 (Th1/Th2) cytokines in the connective tissue disease-associated interstitial pneumonia (CTD-IP).

Methods

A total of 77 CTD-IP patients (CTD-IP group), 60 CTD patients (CTD group), and 50 healthy volunteers (healthy group) examined in our hospital from January 2017 to January 2019 were enrolled for this study. The CTD-IP group was further divided into several subgroups according to the severity of pulmonary ventilation disorder, pulmonary diffuse dysfunction, and the imaging findings of high resolution CT (HRCT). The serum KL-6, Th1 cytokine interferon-γ (IFN-γ), Th2 cytokine interleukin-4 (IL-4) and Th1 / Th2 (IFN-γ/IL-4) levels were compared within the groups and subgroups (P<0.05). Then the values of the above-mentioned serum indicators in assessing the condition of CTD-IP patients were also analyzed.

Results

In the healthy control group, CTD group and CTD-IP group, serum KL-6 and IL-4 levels had an increasing trend, meanwhile, the IFN-γ and IFN-γ/IL-4 levels had a decreasing trend, with statistical significant differences between two groups (P<0.05). In the mild, moderate, and severe pulmonary ventilation disorder subgroups, the serum KL-6 and IL-4 levels had an increasing trend, meanwhile, the IFN-γ and IFN-γ/IL-4 levels had a decreasing trend, with statistical significant differences between two subgroups (P<0.05). In the mild, moderate, and severe pulmonary diffuse dysfunction subgroups, the serum KL-6 and IL-4 levels had an increasing trend, meanwhile, the IFN-γ and IFN-γ/IL-4 levels had a decreasing trend, with statistical significant differences between two subgroups (P<0.05). In the subgroups with different HRCT imaging findings, serum KL-6, IFN-γ, IFN-γ/IL-4 levels were significantly higher in the active group than the inactive group (P<0.05), and IL-4 levels were significantly lower in the active group than the inactive group (P<0.05).

Conclusion

Serum KL-6, IFN-γ, IL-6 and IFN-γ/IL-6 levels have a good application value in reflecting pulmonary ventilation dysfunction, pulmonary diffuse dysfunction, and disease active stage in the patients with CTD-IP, and can be used as reliable serum indicators for assessing the condition of CTD-IP patients.

Key words: Krebs von den Lungen-6, T helper 1/T helper 2 cytokines, Connective tissue disease-associated interstitial pneumonia
表1 三组血清KL-6、IFN-γ、IL-4及IFN-γ/IL-4水平比较(±s)
组　别 例数 KL-6(U/ml) IFN-γ(pg/ml) IL-4(pg/ml) IFN-γ/IL-4
健康对照组 50 176.65±23.58 319.54±50.13 211.62±26.58 1.47±0.36
CTD组 60 216.58±26.51a 246.69±53.33a 253.46±30.16a 0.94±0.27a
CTD-IP组 77 544.42±54.16ab 213.26±41.26ab 286.65±33.67ab 0.76±0.31ab
F值   1 823.821 78.548 96.521 85.661
P值   0.000 0.000 0.000 0.000
表2 不同肺通气障碍分级组血清KL-6、IFN-γ、IL-4及IFN-γ/IL-4水平比较(±s)
组　别 例数 KL-6(U/ml) IFN-γ(pg/ml) IL-4(pg/ml) IFN-γ/IL-4
轻度 26 369.49±42.15 253.69±36.44 243.64±31.26 1.04±0.35
中度 30 523.64±55.47a 213.67±41.25a 267.69±25.53a 0.82±0.25a
重度 21 584.15±76.62ab 153.69±25.47ab 323.44±29.67ab 0.56±0.17ab
F值   87.920 53.003 51.396 20.772
P值   0.000 0.000 0.000 0.000
表3 不同肺弥散功能障碍组血清KL-6、IFN-γ、IL-4及IFN-γ/IL-4水平比较(±s)
组　别 例数 KL-6(U/ml) IFN-γ(pg/ml) IL-4(pg/ml) IFN-γ/IL-4
轻度 33 416.26±44.59 276.46±35.43 244.53±32.17 1.14±0.25
中度 25 544.33±46.67a 226.69±34.56a 271.16±29.54a 0.84±0.21a
重度 19 573.64±63.35ab 173.68±23.64ab 337.49±30.26ab 0.53±0.14ab
F值   65.353 67.010 61.947 56.237
P值   0.000 0.000 0.000 0.000
表4 不同HRCT表现组血清KL-6、IFN-γ、IL-4及IFN-γ/IL-4水平比较(±s)
组　别 例数 KL-6(U/ml) IFN-γ(pg/ml) IL-4(pg/ml) IFN-γ/IL-4
活动性组 37 563.49±73.25 263.66±35.15 235.16±44.52 1.11±0.22
非活动性组 40 513.69±77.54 163.66±26.69 334.16±46.58 0.52±0.11
t值   2.891 14.124 9.518 15.054
P值   0.005 0.000 0.000 0.000
1
Raina A, Benza R, Farber H. EXPRESS: Replacing a phosphodiesterase-5 inhibitor with riociguat in patients with connective tissue disease-associated pulmonary arterial hypertension: A case series[J]. Pulm Circ., 2017, 7(3): 741-746.
2
Tomita M, Ayabe T, Chosa E, et al. Prognostic significance of a tumor marker index based on preoperative serum carcinoembryonic antigen and Krebs von den Lungen-6 levels in non-small cell lung cancer[J]. Asian Pac J Cancer Prev, 2017, 18(1): 287-291.
3
汪　矗，罗　壮，郑圆圆，等. 慢性阻塞性肺疾病患者血清IL-33、IFN-γ表达与Th1/Th2平衡失调[J]. 中国临床研究，2019, 32(5): 624-626.
4
Enomoto Y, Nakamura Y, Colby TV, et al. Radiologic pleuroparenchymal fibroelastosis-like lesion in connective tissue disease-related interstitial lung disease[J]. PLoS One, 2017, 12(6): e0180283.
5
金　金，崔　佳，许小毛，等. 老年人肺通气功能非特异性表现的演变初探[J]. 中华老年医学杂志，2017, 36(4): 417-421.
6
王妍华，蒲　丹，罗　静，等. 147例常见结缔组织病相关间质性肺病的临床特征及转归分析[J]. 西安交通大学学报(医学版), 2019, 40(4): 598-603.
7
Bozena Targońska-Stępniak. Rheumatoid arthritis as a connective tissue disease[J]. Wiad Lek, 2018, 71(1): 47-51.
8
Ferucci ED, Johnston JM, Gordon C, et al. Prevalence of Mixed Connective Tissue Disease in a Population-Based Registry of American Indian/Alaska Native People in 2007[J]. Arthritis Care Res, 2017, 69(8): 1271-1275.
9
王丹清，赵亚雯，孟令超，等. 不同类型结缔组织病骨骼肌损害病理改变分析[J]. 中华风湿病学杂志，2018, 22(5): 328-331,封3.
10
骆　毅，郭春燕，李倩雨，等. 结缔组织病合并肺部真菌感染的临床特点及危险因素分析[J]. 临床肺科杂志，2017, 22(12): 2178-2181.
11
郝燕捷，王　岚，蒋　鑫，等. 结缔组织病相关肺动脉高压合并与不合并肺间质病变患者临床特点与预后的比较[J]. 中华风湿病学杂志，2017, 21(5): 316-321.
12
Kristian Kjellerup Kjeldsen, Wilhelm Weinrebe, Jørgen Bendtsen, et al. Multibeam Bathymetry and CTD-Measurements in two fjord systems in Southeast Greenland[J]. Earth System Science Data, 2017, 9(2): 1-25.
13
Aga Y, Ogi S, Tokunaga Y, et al. Abstract LB-297: In vivo anti-tumor efficacy of UD-017, a novel highly selective & orally available CDK7 inhibitor, in colorectal cancer cells xenograft models[J]. 2017, 77(13 Suppl): LB-297-LB-297.
14
吴　悦，吴　炯，王蓓丽，等. 乳胶凝集法检测唾液酸化糖链抗原KL-6的性能观察及其对间质性肺病的诊断价值[J]. 中国临床医学，2017, 24(5): 759-761.
15
Nakamura T, Nakamura M, Takahashi N. Neonatal high-permeability pulmonary edema based on serial cytokine profiles and KL-6 in serum: case report[J]. Fukushima J Med Sci, 2017, 63(1): 22-27.
16
Nakamura K, Kato M, Miyashita Y, et al. Development of interstitial pneumonia during treatment with eribulin: a case report[J]. BMC Res Notes, 2017, 10(1): 557.
17
刘玉梦，许爱国，赵玉苗，等. 血清KL-6对多发性肌炎/皮肌炎合并肺部疾病的临床价值[J]. 中国实用医刊，2017, 44(10): 10-12.
18
彭　伟，陈　津，魏　伟，等. 血清KL-6预测肺癌患者放疗后发生放射性肺炎风险的研究[J]. 中华放射医学与防护杂志，2017, 37(12): 891-895.
19
张战赛，赵艳芳，唐　亮，等. 大鼠硬金属肺病模型建立及KL-6与TGF-β表达的研究[J]. 中华劳动卫生职业病杂志，2017, 35(4): 293-297.
20
史传见，王思勤，马雪梅，等. 血清KL-6水平在诊断间质性肺疾病中的作用及其敏感性与特异性分析[J]. 徐州医科大学学报，2019, 39(4): 270-272.
21
刘　欣，母齐鸣，王　刚. 慢性乙肝患者外周血PBMC凋亡相关因子和Th1/Th2型细胞因子的水平变化及意义[J]. 临床和实验医学杂志，2019, 18(13): 1394-1397.
22
王　静，景晓娜，牛红青，等. 白细胞介素-2对系统性红斑狼疮辅助性T细胞17及调节性T细胞影响的研究进展[J]. 中华风湿病学杂志，2017, 21(8): 572-574.
23
杨　虹，杨小红，青玉凤，等. 原发性痛风性关节炎患者外周血中辅助性T细胞1/辅助性T细胞2的表达变化及其临床意义[J]. 中华风湿病学杂志，2018, 22(11): 731-736.
24
朱　凯，张爱华，董　令，等. 辅助性T细胞-17与调节性T细胞浸润在砷致大鼠肝脏损伤中的作用[J]. 中华地方病学杂志，2018, 37(7): 536-540.
25
Infantino M, Meacci F, Grossi V, et al. The clinical impact of Anti-DFS70 antibodies in undifferentiated connective tissue disease：case reports and a review of the literature[J]. Immunologic Research, 2017, 65(1): 293-295.
26
Matthew K, Jonathan B, Kaleb A, et al. Lipid droplet formation in Mycobacterium tuberculosis infected macrophages requires IFN-γ/HIF-1α signaling and supports host defense[J]. Plos Pathogens, 2018, 14(1): e1006874.
27
Cristina Capuano, Chiara Pighi, Rosa Molfetta, et al. Obinutuzumab-mediated high affinity ligation of FcγRIIIA/CD16 primes NK cells for IFN-γ production[J]. Oncoimmunology, 2017, 6(3): 10-12.
28
Nikoletta K, Leora H, Min T, et al. Abstract CT159: IFN-γ analysis in blood and tissue as a potential prognostic and/or predictive biomarker[J]. Cancer Res, 2017, 77(13 Supplement): CT159-CT159.
29
Micossé C, von Meyenn L, Sayed Jafari S, et al. 006 TGF-β-and IL-4-induced PPAR-γ promotes IL-9 expression in human TH2 cells[J]. J Invest Dermatol, 2018, 138(5): 11-16.
30
Chatterjee S, Talaat KR, van Seventer EE, et al. Mycobacteria induce TPL-2 mediated IL-10 in IL-4-generated alternatively activated macrophages[J]. Plos One, 2017, 12(6): e0179701.
31
Ritter M, Tamadaho RS, Feid J, et al. IL-4/5 signalling plays an important role during Litomosoides sigmodontis infection, influencing both immune system regulation and tissue pathology in the thoracic cavity[J]. Int J Parasitol, 2017, 47(14): 951-960.
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