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浙江大学学报(医学版)  2016, Vol. 45 Issue (3): 281-286    DOI: 10.3785/j.issn.1008-9292.2016.05.11
原著     
非全身型幼年特发性关节炎患儿外周血T辅助细胞1/2细胞因子水平分析
姜丽娇1,2, 卢美萍1, 郭莉1, 吴建强1, 邹丽霞1, 徐益萍1
1. 浙江大学医学院附属儿童医院风湿免疫变态反应科, 浙江 杭州 310003;
2. 浙江省台州医院儿科, 浙江 临海 317000
Serum levels of Th1/Th2 cytokines in children with non-systemic juvenile idiopathic arthritis
JIANG Lijiao1,2, LU Meiping1, GUO Li1, WU Jianqiang1, ZOU Lixia1, XU Yiping1
1. Department of Rheumatology Immunology & Allergy, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China;
2. Department of Pediatrics, Zhejiang Taizhou Hospital, Linhai 317000, Zhejiang Province, China
全文: PDF(1012 KB)  
摘要: 

目的:分析非全身型幼年特发性关节炎(SOJIA)患儿外周血T辅助细胞1/2(Th1/Th2)细胞因子水平变化特点,了解相关病理机制,以期为治疗决策提供依据。方法:收集2012年11月至2015年5月浙江大学医学院附属儿童医院活动期非SOJIA患儿41例(非SOJIA组,n=41)的临床资料,其中多关节炎型11例,少关节炎型10例,附着点炎型20例。采用流式细胞术检测患儿血清IL-2、IL-4、IL-6、IL-10、TNF-α和γ干扰素水平,并与同期85例活动期SOJIA患儿及202名健康体检儿童(正常对照组,n=202)比较,同时分析非SOJIA患儿血清细胞因子水平与红细胞沉降率、C反应蛋白的相关性。结果:与正常对照组比较,非SOJIA组患儿血清IL-2、IL-6、γ干扰素升高(2.9 pg/mL与2.6 pg/mL,9.9 pg/mL与6.4 pg/mL,6.3 pg/mL与5.1 pg/mL,均P<0.05),而TNF-α、IL-10降低(2.7 pg/mL与3.9 pg/mL,2.9 pg/mL与7.1 pg/mL,均P<0.01);与SOJIA组比较,非SOJIA组IL-6、IL-10降低(9.9 pg/mL与33.5 pg/mL,2.9 pg/mL与4.1 pg/mL,均P<0.01),IL-4、γ干扰素升高(3.1 pg/mL与2.3 pg/mL,6.3 pg/mL与4.4 pg/mL,均P<0.05)。同时非SOJIA组附着点炎型、多关节炎型患儿血清IL-6水平高于少关节炎型(12.7 pg/mL、11.0 pg/mL与4.2 pg/mL,均P<0.05);附着点炎型患儿血清IL-6、TNF-α水平与超敏CRP呈正相关。结论:非SOJIA患儿Th1/Th2细胞因子失衡且Th1细胞占优势,血清IL-6可能参与非SOJIA的发病机制。

关键词 关节炎,幼年型类风湿/病理生理学Th1细胞/免疫学Th2细胞/免疫学干扰素Ⅱ型/血液细胞因子类/血液肿瘤坏死因子α/血液白细胞介素类/血液    
Abstract

Objective: To investigate the serum levels of Th1/Th2 cytokines in children with non-systemic juvenile onset idiopathic arthritis (non-SOJIA). Methods: Clinical data of 41 children with non-SOJIA, including 11 cases of polyarthritis, 10 cases of oligoarthritis and 20 cases of enthesitis related JIA (ERA), admitted in Children's Hospital of Zhejiang University School of Medicine during November 2012 and May 2015 were retrospectively analyzed. Serum levels of Th1/Th2 cytokines including IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ were measured by flow cytometry in patients with non-SOJIA, and compared with those in patients with SOJIA (SOJIA group, n=85) and healthy children (control group, n=202); their correlations with erythrocyte sedimentation rate and C reactive protein and CRP were analyzed. Results: Compared with the healthy control group, serum levels of IL-2, IL-6 and IFN-γ were significantly increased in patients with non-SOJIA (2.9 vs. 2.6 pg/mL, 9.9 vs. 6.4 pg/mL, 6.3 vs. 5.1 pg/mL, allP<0.05),while levels of TNF-α and IL-10 were significantly decreased (2.7 vs. 3.9 pg/mL, 2.9 vs. 7.1 pg/mL, both P<0.01). Compared with the SOJIA group, serum levels of IL-6 and IL-10 were significantly decreased in patients with non-SOJIA (9.9 vs. 33.5 pg/mL, 2.9 vs. 4.1 pg/mL, both P<0.01), while levels of IL-4 and IL-10 were significantly increased (3.1 vs. 2.3 pg/mL, 6.3 vs. 4.4 pg/mL, both P<0.05). Serum levels of IL-6 in patients with polyarthritis or ERA were higher than that in patients with oligoarthritis (12.7 and 11.0 vs. 4.2 pg/mL, both P<0.05). A positive correlation of IL-6 or TNF-α level with C reactive protein was observed in patients with ERA. Conclusions: The results indicate that Th1/Th2 imbalance and Th1 predominance may exist in children with non-SOJIA; and IL-6 may be involved in the pathogenesis of non-SOJIA children with polyarthritis.

Key wordsArthritis, juvenile rheumatoid/physiopathology    Th1 cells/immunology    Th2 cells/immunology    Interferon type II/blood    Cytokines/blood    Tumor necrosis factor-alpha /blood    Interleukins/blood
收稿日期: 2016-01-11
CLC:  R593.2  
基金资助:

国家自然科学基金(81270067)

通讯作者: 卢美萍(1966-),女,博士,主任医师,硕士生导师,从事呼吸系统、风湿免疫过敏性疾病研究;E-mail:meipinglu@126.com;http://orcid.org/0000-0002-3264-6397     E-mail: meipinglu@126.com
作者简介: 姜丽娇(1982-),女,学士,主治医师,从事儿童风湿免疫学研究;E-mail:jianglijiao@enzemed.com;http://orcid.org/0000-0001-7511-0093
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姜丽娇 等. 非全身型幼年特发性关节炎患儿外周血T辅助细胞1/2细胞因子水平分析[J]. 浙江大学学报(医学版), 2016, 45(3): 281-286.
JIANG Lijiao, LU Meiping, GUO Li, WU Jianqiang, ZOU Lixia, XU Yiping. Serum levels of Th1/Th2 cytokines in children with non-systemic juvenile idiopathic arthritis. Journal of ZheJiang University(Medical Science), 2016, 45(3): 281-286.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2016.05.11      或      http://www.zjujournals.com/xueshu/med/CN/Y2016/V45/I3/281

[1] 何晓琥. 幼年特发性关节炎——国际风湿病学会联盟新分类标准讨论稿[J]. 中华儿科杂志, 2002, 40(4): 65-66. HE Xiaohu. Juvenile idiopathic arthritis, new classification standard discussion of the rheumatism association international union[J]. Chinese Journal of Pediatrics, 2002, 40(4): 65-66. (in Chinese)
[2] LIN Y T,WANG C T,GERSHWIN M E,et a1.The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis[J].Autoimmun Rev,2011,10(8):482-489.
[3] NIRMALA N, GROM A, GRAM H. Biomarkers in systemic juvenile idiopathic arthritis: a comparison with biomarkers in cryopyrin-associated periodic syndromes[J]. Curr Opin Rheumatol,2014,26(5): 543-552.
[4] 郭莉,卢美萍,汤永民,等. 新发活动期全身型幼年特发性关节炎血清细胞因子水平分析[J]. 中国当代儿科杂志, 2014, 16(12): 1241-1244. GUO Li, LU Meiping, TANG Yongmin, et al. Serum cytokine levels in children with newly diagnosed active systemic juvenile idiopathic arthritis[J]. Chinese Journal of Contemporary Pediatrics, 2014, 16(12): 1241-1244. (in Chinese)
[5] DOODES P D,CAO Y, HAMEL K M, et al. IFN-gamma regulates the requirement for IL-17 in proteoglycan-induced arthritis[J]. J Immunol, 2010, 184(3):1552-1559.
[6] NIU Q, CAI B, HUANG Z C, et al. Disturbed Th17/Treg balance in patients with rheumatoid arthritis[J]. Rheumatolo Int, 2012, 32(9):2731-2736.
[7] LUBBERTS E. Role of T lymphocytes in the development of rheumatoid arthritis. Implications for treatment[J]. Curr Pharm Des, 2015, 21(2):142-146.
[8] NISHIMOTO N,KISHIMOTO T.Intedeukin 6:from bench to bedside[J].Nat Clin Pract Rheumatol, 2006, 2(11): 619-626.
[9] YOKOTA S,TANAKA T, KISHIMOTO T. Efficacy, safety and tolerability of tocilizumab in patients with systemic juvenile idiopathic arthritis[J]. Ther Adv Musculoskelet Dis,2012,4(6):387-397.
[10] STAGI S, CAVALLI L, SIGNORINI C, et al. Bone mass and quality in patients with juvenile idiopathic arthritis: longitudinal evaluation of bone-mass determinants by using dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and quantitative ultrasonography[J]. Arthritis Res Ther, 2014, 16(2): R83.
[11] OSTA B, BENEDETTI G, MIOSSEC P. Classical and paradoxical effects of TNF-α on bone homeostasis[J]. Front Immunol, 2014,13(5):48.
[12] MCINNES I B, BUCKLEY C D, ISAACS J D.Cytokines in rheumatoid arthritis-shaping the immunological landscape[J]. Nat Rev Rheumatol, 2016, 12(1): 63-68.
[13] GRAVALLESE E M, GOLDRING S R. Cellular mechanisms and the role of cytokines in bone erosions in rheumatoid arthritis[J]. Arthritis Rheum, 2000, 43(10): 2143-2151.
[14] MAKHIJA R, KINGSNORTH A N. Cytokine storm in acute pancreatitis[J]. J Hepatobiliary Pancreat Surg, 2002, 9(4): 401-410.
[15] 尹薇, 丁艳, 刘凡, 等. 幼年特发性关节炎患儿基质金属蛋白酶及细胞因子的改变及意义[J].中华风湿病学杂志,2013, 17(9): 601-605. YIN Wei, DING Yan, LIU Fan, et al. Changes of matrix metalloproteinase angcytokin-es and its clinical significance in children with juvenile idiopathic arthritis[J].Chinese Journal of Rheumatology, 2013, 17(9): 601-605.(in Chinese)
[16] TRACEY D, KLARESKOG L, SASSO E H, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review[J]. Pharmacol Ther, 2008, 117(2): 244-279.
[17] WEDDERBURN L R, ROBINSON N, PATEL A, et al. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis[J]. Arthritis Rheum, 2000, 43(4): 765-774.
[18] LUBBERTS E, JOOSTE L A, CHABAUD M, et al. IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion[J]. J Clin Invest, 2000,105(12): 1697-1710.
[19] SABAT R, GRVTZ G, WARSZAWSKA K, et al. Biology of interleukin-10[J]. Cytokine Growth Factor Rev, 2010, 21(5):331-344.
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