血清IgG4和TGF-β1及CTGF水平与桥本甲状腺炎纤维化的相关性

Correlation btween IgG4, TGF-β1, CTGF and fibrosis in Hashimoto thyroiditis

目的探讨桥本甲状腺炎（HT）患者血清免疫球蛋白G4（IgG4）、转化生长因子p1（TGF-β1）和结缔组织生长因子（CTCF）水平与甲状腺纤维化的相关性。方法病例对照研究。选取2013年5月至2015年3月武汉协和医院就诊的159例HT患者，按IgG4水平分为IgC4组（IgG4≥1．35g／L，39例）和非IgG4组（IgG4〈1．35g/L，120例）。采用ELISA法测定血清1gG4、TGF—β1、CTGF水平，采用电化学发光法测定血清甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TgAb），并行甲状腺超声检查。采用SPSS17．0软件进行统计学分析，Mann—WhitneyU检验比较两独立样本的非正态分布资料，Fisher精确检验比较甲状腺影像差异，相关性检验分析IgG4与各指标的关系，多因素Logistic回归分析甲状腺纤维化的危险因素。结果与非IgG4组比较，IgG4组：TPOAb[（455．2±169．7）vs．（186．5±102．3），U=27．0，P=0．003]、TgAb[（984．6±452．7）vs．（289．3±245．1），U=30．5，P=0．017]、TGF—B1[（1．45±0．97）vs．（0．30±0．22），U=119．0，P=0．035]、CTGF[（88．65±14．39）vs．（62．21±8．76），U=69．0，P=0．039]均显著升高，超声显示甲状腺纤维化信号增强（35／4 vs 32／88，X2=48．03，P=0．000），差异有统计学意义；IgG4与TPOAb（r=0．719，P=0．000）、CTGF与TGF—β1呈显著正相关（r=0．500，P〈0．01）；多因素Logistic回归分析显示IgG4、TPOAb、TGF-β1、CTGF均为甲状腺纤维化形成的危险因素，IgC4：风险比（OR）=1．968，P=0．014，95％CI=1．287～2．041；TPOAb，OR=2．537．P=0．012，CI=I．322—2．869；TGF—β1：OR=1．549，P=0．023，叫：1．105～1．498：CTGF，OR=1．185，P=0．046，CI=1．204-1．625。结论较高的循环抗体和IgG4、TCF—β1、CTGF水平是HT纤维化形成的独立危险因素，与甲状腺纤维化显著相关。

Objective To explore the correlation among serum immunoglobulin G4 （IgG4）, transforming growth factor-β1（TGF-β1）, connective tissue growth factor （CTGF） and Hashimoto thyroiditis （HT） thyroid fibrosis. Methods Case-control study. A total of 159 patients with HT visiting the Wuhan Union Hospital were collected from May 2013 to March 2015. All patients were divided into IgG4 HT group （lgG4 ≥1.35 g/L, n = 39） and non-IgG4 HT group （IgG4 〈 1.35 g/L, n = 120）. The serum IgG4, TGF- β1 and CTGF were determined by enzyme-linked immunosorbent assays. The levels of serum thyroid peroxidase antibodies （ TPOAb ） and thyroglobulin antibodies （ TgAb ） were measured by electrochemiluminescence immunoassay. Meanwhile, ultrasound of the thyroid gland was performed. Statistical analysis was performed by use of SPSS 17.0 software. The Mann-Whitney U test was used to compare two independent samples of non-normal distribution data, Fisher＇s exact test was employed to analyze thyroid imaging differences, correlation test was performed to examine various correlations, multivariate Logistic regression analysis was used to evaluate thyroid fibrosis risk factors. Results Compared with that of non-IgG4 HT group, IgG4 HT group ： TPOAb [ （ 455.2±169.7 ） vs. （ 186. 5±102. 3 ）, U = 27.0, P=0.003], TgAb [（984.6±452.7） vs. （289.3±245.1）, U=30.5, P=0.017], TGFq31 [ （ 1.45±0. 97） vs. （0.30±0. 22）, U=119. 0, P = 0. 035] and CTGF [ （88.65±14. 39） vs. （62. 21±8.76 ）, U = 69. 0, P = 0. 039 ] were significantly higher, thyroid ultrasound showed obvious fibrosis （ 35/4 vs. 32/88, X2 =48. 03, P = 0. 000） ; significant positive linear correlation between IgG4 and TPOAb （r = 0. 719, P =0. 000） , CTGF and TGF-β1 （r =0. 500, P 〈0. 01 ） respeetively. Logistic regression analysis indicated that all the serum IgG4, TPOAb, TGF-[31 and CTGF were independent risk factors of thyroid fibrosis [ IgG4, odds ratio （OR） = 1. 968, P = 0. 014, 95% confidence interval （CI） = 1. 287 - 2. 041 ; TPOAb, OR =2. 537, P =0. 012, CI = 1. 322 -2. 869; TGF-β1, OR = 1. 549, P =0. 023, C1 = 1. 105 - 1. 498 ; CTGF, OR = 1. 185, P = 0. 046, CI = 1. 204 - 1. 625 ]. Conclusion The highlevel of eirculating antibodies, IgG4, TGF-~I and CTGF were signifieantly associated with thyroid fibrosis, and were independent risk factors of HT fibrosis.