不同类型自身免疫性甲状腺疾病Th1/Th2平衡偏移的初步探讨

Preliminary Study of Th1 / Th2 Imbalance in Different Types of Autoimmune Thyroid Disease

目的初步探讨Th1/Th2平衡偏移在不同类型自身免疫性甲状腺疾病(AITD主要为Graves病和桥本甲状腺炎)中的作用机制和不同病程阶段的变化。方法选取HT患者60例,GD患者60例,非毒性结节性甲状腺肿患者20例及健康体检者20例作为研究对象,各组间性别比例及年龄比较无统计学差异。通过ELISA法检测外周血清中Th1趋化因子(CXCL10)及Th2趋化因子(CCL22)的含量,比较各组间及不同病程阶段血清CXCL10、CCL22水平及二者(CXCL10/CCL22)比值有无差异;分析血清CXCL10、CCL22及二者比值与甲功(TT3、TT4、FT3、FT4、TSH)、甲状腺自身抗体(TPOAb、TGAb、TRA)及炎症因子(ESR、CRP)的相关性。结果 AITD患者血清CXCL10、CCL22水平及二者比值高于结节性甲状腺肿患者及正常体检者(P<0.05),后两者间差异无统计学意义。GD(疗程小于3个月者)患者血清CCL22水平明显高于HT者,而CXCL10/CCL22明显低于HT者(P<0.05),两组血清CXCL10水平比较,差异无统计学意义。初发AITD患者与复发者比较Th1/Th2趋化因子水平及比值差异无统计学意义,药物治疗稳定后,AITD患者血清趋化因子水平及比值有所下降,但仍高于正常体检者。血清CXCL10、CCL22水平及二者比值与TPOAb、TGAb、TRAb、CPR、ESR及甲状腺体积呈正相关,与FT3、FT4、TSH无相关性。结论 Th1及Th2共同参与了AITD的发病,但以Th1为主。HT与GD患者Th1/Th2偏移有所不同,后者Th2免疫异常更为显著,且经药物治疗后,GD患者Th1/Th2平衡恢复较HT者更为明显。

Objective To investigate the mechanisms that Thl/Th2 imbalance contributes to the autoimmune thyroid disease（HT and GD） and the variation of the imbalances in different stage. Methods A total of 60 autoimmune thyruiditis （Including the course within 3 months 30 and above 3 months 30） ,60 Graves disease patients （Including the course within 3 months 30 and above 3 months 30） ,20 nontoxic muhinodular goiter patients and 20 healthy controls were objects of this study. The four groups were similar in gender distribution and age. In all subjects we measured serum levels of Thl - associated （ C - X - C motif） ligand 10（CXCL10） and Th2 - associated （ C - C motif） ligand 22（CCL22） by ELISA, moreover, calculated the ratio of CXCL10/CCL22, compareed the levels of CXCL10, CCL22 and the ratio among four groups and analyzed the correlation CXCL10, CCL22 or the ration of two between TT3,TTg, FTS, FT4, TSH,TPOAb,TGAb,TRAb, ESR, CRP and the thyroid volume. Results Patients with AITD showed higher levels of serum CXCL10, CCL22 and the ratio compared with the nontoxic muhinodular goiter patients and healthy controls（ P 〈 0.05 ）. The latter two had no significant statistical difference. Patients with GD （ the course within 3 months） showed significant higher levels of serum CCL22 and lower ratio than HT patients, but the levels of CXCL10 had no significant statistical difference between them. The newly diagnosed and recurring AI- TD had no significant statistical difference in levels of Thl/Th2 - associated chemokines and the ratio. After drug therapy, there was reduction in levels of chemokines and ratio in AITD, but still higher than healthy controls. No correlation was found between levels of CX- CL10,CCL22 or the ratio and FT3 ,FT4 or TSH at any time point, but significant positive correlation was shown between CXCL10,CCL22 or the ratio and TPOAb,TGAb,TRAb,ESR,CRP and the thyroid volume. Conclusion The results indicate that both Thl and Th2 be involved in the morbidity of AITD, but Thl had absolute predominance. There was some difference in Thl/Th2 imbalances between HT and GD. The latter showed more obvious Th2 dysimmunity. Thl/Th2 imbalance resumed more tangible in patients with GD after treatment.