甲状腺球蛋白及其抗体在自身免疫性甲状腺病中的作用

甲状腺球蛋白（ Ｔｇ ） 是主要由甲状腺滤泡细胞合成的一种粘蛋白， 其抗原性与 Ｔｇ 单体的糖基化、碘有机化等密切相关。 Ｔｇ 的抗原性与自身免疫性甲状腺疾病（ Ａ Ｉ Ｔ Ｄ） 的发生有关。 Ｔｇ 的胰蛋白酶解片段可诱发实验性的免疫性甲状腺炎。 Ａ Ｉ Ｔ Ｄ 病人体内抗 Ｔｇ 抗体是针对不同 Ｔｇ 抗原产生的， 其对 Ｔｇ 抗原表位有限制性的识别。体内抗 Ｔｇ 抗体升高可导致甲状腺本身的破坏， 在 Ａ Ｉ Ｔ Ｄ 的发病中有一定的作用。     

TGA和TPO-Ab在自身免疫性甲状腺疾病诊断中的意义

本文旨在分析甲状腺球蛋白抗体（TGA）和抗过氧化物酶抗体（TPO—Ab）在Graves’病（GD）、桥本氏甲状腺炎（HT）和非自身免疫性甲状腺疾病中的分布特点和差异,以及两个抗体增高程度与甲状腺激素变化的关系。     

TGA、TPO-Ab、TRAb和TSH在自身免疫性甲状腺病中的临床应用

目的：探讨TGA、TPO-Ab、TRAb和TSH在自身免疫性甲状腺病中的诊断和鉴别诊断价值。方法：采用化学发光法检测80例自身免疫性甲状腺病患者（桥本甲状腺炎40例,Graves病40例）、50例甲状腺结节患者和40例正常对照者血清TGA、TPO-Ab、TRAb和TSH水平,通过ROC曲线评估最佳诊断阈值。结果：自身免疫性甲状腺病（桥本甲状腺炎和Graves病）患者与非自身免疫性甲状腺疾病（甲状腺结节）患者血清TGA、TPO-Ab的差异有统计学差异（P〈0.01）,非自身免疫性甲状腺病患者组与正常对照组比较无统计学意义（P〉0.05）。在自身免疫性甲状腺病患者中,Graves病患者TRAb水平高于桥本甲状腺炎患者（P〈0.01）,而TSH水平低于桥本甲状腺炎患者（P〈0.01）。通过ROC曲线分析,当TGA、TPO-Ab分别为70.2U/ml、105.65IU/ml时,对自身免疫性甲状腺病的诊断具有最高的灵敏度和特异性;当TRAb、TSH分别为2.25IU/ml、0.60μlU/ml时,对Graves病和桥本甲状腺炎的鉴别诊断价值最高。实验室建立的参考值与试剂盒提供的参考值比较,具有更高的特异性。结论：TGA和TPO-Ab对自身免疫性甲状腺病的诊断具有重要意义,而TRAb和TSH对鉴别诊断Graves病和桥本甲状腺炎具有重要的临床应用价值。每个实验室有必要建立自己的参考范围,为临床和病人提供更准确、有效的信息。     

TPO/TPO抗体与自身免疫性甲状腺疾病的研究进展

自身免疫性甲状腺疾病（AITD）是临床上常见的一种器官特异性自身免疫性疾病，其发病受遗传背景、免疫系统和环境条件等多种因素的影响，表现甲状腺功能异常，特别是甲状腺细胞上的甲状腺过氧化物酶（Thyroiperoxidase，TPO）不仅参与甲状腺激素的合成、分泌，也是诱发AITD的重要自身抗原，TPO和TPO自身抗体（TPOAb）介导AITD的发生。为此，本文就TPO和TPOAb与AITD发病的研究进展加以综述。     

自身免疫性甲状腺疾病患者血清TPO-Ab测定的临床应用

自身免疫性甲状腺疾病（autoimmune thyroid disease,AI-TD）主要包括Graves＇病（GD）和桥本甲状炎（HT）,有关AI-TD的发病机制迄今尚未阐明。甲状腺过氧化物酶抗体（TPO-Ab）是主要的甲状腺组织自身抗体,与甲状腺组织免疫性损伤密切相关。本文对177例AITD患者和64例非AI-TD患者进行了血清TPO-Ab的测定,现报道如下。     

抗人甲状腺过氧化物酶抗体与其他自身抗体的关系

甲状腺过氧化物酶（ＴＰＯ）是甲状腺微粒体的抗原成分。在纯化抗原建立测定抗ＴＰＯ抗体ＥＬＩＳＡ法的基础上，并对抗ＴＰＯ与其他自身抗体的伴随关系作了研究。发现除自身免疫性甲状腺病有较高阳性率外，ＳＬＥ等患者抗ＴＰＯ检出率也很高（１０％￣５２．１％），且抗ＴＰＯ阳性者，抗核抗体等其他自身抗体的阳性率也高达３０．８％￣９５．２％。抗ＴＰＯ抗体与其他自身抗体的相关系数ｒ＝０．７４６７（Ｐ〈０．０１）。     

淋巴细胞在自身免疫性甲状腺疾病中的研究进展

弥漫性毒性甲状腺肿(Graves disease, GD)和桥本甲状腺炎(Hashimoto thyroiditis, HT)都是遗传易感儿童在感染、应激、药物以及性激素等环境危险因素影响下出现的,并伴有大量淋巴细胞浸润的自身免疫性疾病。其中,GD是导致儿童甲状腺功能亢进的最常见病因,约占全部自身免疫性甲状腺疾病病例的95%。目前,已有大量研究对淋巴细胞在GD和HT患者的甲状腺激发免疫损伤的机制进行了探索。该文总结T、B细胞在GD和HT中的免疫损伤机制以及炎性因子和甲状腺相关抗体对淋巴细胞的调节作用,旨在为用淋巴细胞监测GD和HT的治疗和预后研究提供新思路。     

甲状腺自身抗体对甲状腺结节良、恶性的鉴别诊断意义

目的：探讨甲状腺球蛋白抗体(TgAb)和甲状腺过氧化物酶抗体(TPOAb)在甲状腺结节良、恶性的鉴别诊断中的意义。方法收集新疆医科大学第一附属医院血管甲状腺外科行手术治疗的170例甲状腺癌患者和200例结节性甲状腺肿患者,回顾性分析两组的临床资料。结果年龄、民族、TgAb、TPOAb这四个指标在病例组和对照组中的差异有统计学意义(<0.05)。结论 TgAb、TPOAb对鉴别甲状腺结节的良、恶性有一定的临床意义。     

TPO-Ab及TGA与淋巴细胞亚群联检在AITD中的临床价值

目的:探讨自身免疫性甲状腺疾病(AITD)发病与甲状腺自身抗体之间存在的作用关系.方法:分别采用电化学发光法(ECL)检测了甲状腺过氧化物酶抗体(TPO-Ab)水平,采用放射免疫分析检测了89例男性及81例女性AITD患者和相应正常对照组的甲状腺球蛋白抗体(TGA),并采用免疫荧光标记单克隆抗体和流式细胞仪联检T淋巴细胞亚群(CD4 /CD8 )的活性.结果:AITD患者TPO-Ab以及TGA的水平均显著高于对照组(P＜0.01),相关分析显示,抗体水平与淋巴细胞T细胞亚群(CD4 /CD8 )活性变化没有明显相关(P＞0.05).结论:甲状腺自身抗体的水平变化可作为AITD部分病因的推测和提示.     

1171例甲状腺疾病患者TMA,TGA检测的临床意义

本文对1994～1998年确诊的1171例甲状腺疾病患者作了TGA(甲状腺球蛋白抗体),TMA(甲状腺微粒体抗体)的联合测定,以探讨其临床意义。 材料和方法 一、对象:正常组:均为我院门诊体检合格的健康人228例(女158,男70)。年龄9～55岁。甲状腺疾病组1171例(男271,女900)。其中桥本氏甲状腺炎236例(男80,女156),桥本氏甲亢142例(男13,女129),甲亢368例(男92,女256),甲减126例(男21,女105),单纯甲肿213例(男51,女162),甲状腺瘤86例(男35,女51)。均系门诊及住院的已确诊的     

Low Serum Vitamin D Is Associated with Anti-Thyroid Peroxidase Antibody in Autoimmune Thyroiditis

Purpose

The association between autoimmune thyroid diseases (AITDs) and vitamin D deficiency is controversial. We aimed to evaluate the relationship between serum 25-hydroxy-vitamin D₃ [25(OH)D₃] and anti-thyroid antibody levels.

Materials and Methods

25(OH)D₃, anti-thyroid antibodies, and thyroid function measured in 304 patients who visited the endocrinology clinic were analyzed. The patients were subgrouped into the AITDs or non-AITDs category according to the presence or absence of anti-thyroid antibodies. The relationship between anti-thyroid peroxidase antibody (TPOAb) and 25(OH)D₃ was evaluated.

Results

The patients with elevated anti-thyroid antibodies had lower levels of serum 25(OH)D₃ than those who did not (12.6±5.5 ng/mL vs. 14.5±7.3 ng/mL, respectively, p<0.001). Importantly, after adjusting for age, sex, and body mass index, a negative correlation (r=-0.252, p<0.001) was recognized between 25(OH)D₃ and TPOAb levels in the AITDs group, but this correlation did not exist in the non-AITDs group (r=0.117, p=0.127). 25(OH)D₃ level was confirmed as an independent factor after adjusting for co-factors that may affect the presence of TPOAb in the AITDs group.

Conclusion

25(OH)D₃ level is an independent factor affecting the presence of TPOAb in AITDs. The causal effect of 25(OH)D₃ deficiency to AITDs is to be elucidated.     

Thyroid peroxidase and the induction of autoimmune thyroid disease

Animal models of autoimmune thyroid disease are associated with thyroglobulin (Tg) as autoantigen whereas in man the autoimmune response to microsomal antigen/thyroid peroxidase (TPO) appears to play a major role in thyroiditis. Consequently, we have compared the ability of TPO and Tg to induce thyroid autoantibodies and thyroid damage in mice known to be susceptible (CBA/J) or resistant (BALB/c) to thyroiditis induced using murine Tg. Groups of three to five mice were immunized twice using Freund's complete adjuvant with 80-100 micrograms highly purified porcine (p) TPO, pTg, rat (r) Tg, human Tg, bovine serum albumin (BSA) or BSA + 0.2 micrograms pTg (the level of Tg contamination of TPO). Four weeks after immunization with TPO, plasma from CBA/J (but not BALB/c) mice contained IgG class antibodies which bound to TPO-coated tubes in the presence or absence of excess Tg (and could therefore be clearly distinguished from Tg antibodies) but there was no evidence of thyroiditis in either strain of mice. In contrast, in CBA/J mice immunized with rTg and, to a lesser extent in mice that had received pTg, thyroid tissue was infiltrated with lymphoid cells and/or neutrophils and antibodies to pTg (but not pTPO) were present. Our observations demonstrate that induction of TPO antibody alone is insufficient to lead to thyroiditis in CBA/J mice. Further, these studies emphasize the complex interactions between MHC and different thyroid antigens in the processes leading to thyroid destruction.     

产后自身免疫性甲状腺功能失调患者血清甲状腺抗体的临床意义

目的 探讨产后自身免疫性甲状腺功能失调患者血清TPOAb、TRAb的临床意义.方法 检测66例产后自身免疫性甲状腺功能失调患者血清TPOAb、TRAb浓度.患者依就诊结果分为:产后甲状腺炎组,产后Graves病组.结果 产后Graves病17例,TPOAb阳性率64.7％(11/17);产后甲状腺炎49例,TPOAb阳性率81.6％ (40/49),两组数值均远高于妊娠妇女3％ ～ 10％ TPOAb阳性率,但产后Graves病组TPOAb阳性率与产后甲状腺炎组比较无明显统计学差异(P＞0.05).产后Graves病TRAb阳性率70.6％(12/17),产后甲状腺炎组TRAb检测均为阴性,两组间有明显差别(P＜0.05).结论 TPOAb及TRAb可用于产后自身免疫性甲状腺功能失调的检测.TRAb可作为鉴别产后Graves病和产后甲状腺炎的重要的检测项目.     

Thyroid Peroxidase Expression in Diseased Human Thyroid Glands

Histoenzymologic studies of the human thyroid have been restricted to attempts to differentiate benign from malignant tumors and, to our knowledge, there is no systematic study on the distribution and behavior of enzymes for several types of lesions of the thyroid gland. The aim of the present study was to investigate thyroid peroxidase (TPO) expression in diseased thyroids, as well as to study the role of this enzyme as a parameter to define the biological behavior of thyroid lesions. A total of 117 neoplastic and nonneoplastic lesions of the thyroid were evaluated. The expression of TPO was determined by the analysis of at least 200 cells/specimen. A rate of 80% of positive cells was considered a threshold for TPO positivity. TPO expression was detected in all nonneoplastic lesions of thyroid as well as in 78.8% of the adenomas. We also observed positivity for TPO in 20% of malignant lesions. Therefore, these findings do not allow separation of benign and malignant lesions of the thyroid based in the expression of TPO. Presented at the XXI International Congress of the International Academy of Pathology and 12th World Congress of Academic and Environmental Pathology, Budapest, Hungary, 20–25 October 1996.     

甲状腺激素与瘦素分泌关系的探讨

目的:探讨甲状腺功能与瘦素分泌的关系。方法:正常甲状腺功能组75例、甲状腺功能亢进组44例、甲状腺功能减退组27例,分别检测血清甲状腺功能指标和瘦素浓度。结果:甲状腺功能正常组、甲状腺功能亢进组和甲状腺功能减退组的血清瘦素浓度分别为(5.40±3.78)ng/ml、(5.99±5.24)ng/ml和(5.59±4.23)ng/ml,三组瘦素浓度无明显差别。血清瘦素浓度与TSH浓度呈正相关(r=0.27,P<0.01)。结论:甲状腺功能状态对瘦素分泌无明显影响,瘦素浓度与TSH有正相关关系。     

甲状腺激素联合甲状腺过氧化物酶抗体在产前筛检中的临床意义

目的 探讨产前筛检中甲状腺激素联合甲状腺过氧化物酶抗体(TPOAb)的临床意义.方法 选取我院2014年1月至2015年1月进行产检及分娩的孕妇共420例,检测其FT4、FT3、TSH和TPOAb水平,根据检测结果分为四组:甲功正常、TPOAb阴性(A组),甲功正常、TPOAb阳性(B组),甲功低下、TPOAb阴性(C组)和甲功低下、TPOAb阳性(D组).对比不同TPOAb及甲功孕妇的甲状腺激素水平、孕周及新生儿一般情况和妊娠并发症发生率.结果 A组和B组的FT3、FT4和TSH水平无显著差异(P＜0.05);C组、D组的FT3、FT4显著低于A组、B组,TSH显著高于A组、B组(P＜0.05);D组的FT3、FT4显著低于C组,TSH显著高于C组(P＜0.05).A组和B组的孕周及新生儿一般情况无显著差异(P＜0.05);C组、D组的新生儿胸围显著低于A组、B组,新生儿体重和新生儿头围显著高于A组、B组(P＜0.05);D组的新生儿胸围显著低于C组,新生儿体重和新生儿头围显著高于C组(P＜0.05).B组、C组的胎儿宫内发育迟缓率显著高于A组(P＜0.05),其他并发症在各组之间无显著差异(P＞0.05).结论 甲状腺激素联合TPOAb和产科并发症具有一定相关性,孕期筛查并及时治疗有助于改善妊娠结局和胎儿预后.     

血清TGAb的测定在分化型甲状腺癌中的作用

探讨在电化学发光免疫法测定TG时TGAb对其测定的影响及TGAb在分化型甲状腺癌（DTC）患者中的阳性分布情况。在一高浓度的TGAb血清中加入一定量的高浓度TG（试剂R3）,测定TG的回收率,并对74例DTC患者在术前及术后一个月分别进行TG和TGAb的测定。结果显示,TGAb的浓度在2840.20～81.15IU/mL之间时,TG的回收率在73.99%～93.34%之间,TG的回收率同TGAb的浓度呈负相关（r=-0.9909,P〈0.01）;TGAb在DTC患者中的阳性率为29.7%,其中以乳头状癌伴桥本甲状腺炎组为最高（56.5%）。结论：在用电化学发光免疫法测定TG时TGAb会对其产生负干扰,并呈浓度依赖性,且TGAb在DTC患者中存在一定的阳性率,这应引起临床的重视,以防发生错误的临床诊断。     

Increase in Serum Concentration of FAS Ligand as a Possible Mechanism for Antithyroid Cytotoxicity during Autoimmune Thyroid Diseases

We studied the effect of combination treatment with T-activin and vitamin E on acute toxicity and antitumor activity of cyclophosphamide in mice. Combined administration of these preparations 1.37-fold increased the maximum permissible dose of cyclophosphamide without affecting its LD(50)and delayed mouse death from cyclophosphamide toxicity. Most mice died only 3 days after combination treatment with the test preparations and cyclophosphamide in doses of LD(16)-LD(84). The second peak of death from hematologic toxicity of cyclophosphamide was absent under these conditions. T-activin and vitamin E did not abolish the antitumor effect of cyclophosphamide on mice with subcutaneously implanted P-388 lympholeukemia. Tumor growth was suppressed by 100%.     

硒对TPOAb的影响研究进展及其在甲状腺疾病中的应用

硒是人体必需的微量元素,近年来,硒与自身免疫性甲状腺炎的关系引起了越来越多的医学研究者的关注。甲状腺过氧化物酶抗体（thyroid peroxidase antibody,TPOAb）是甲状腺免疫性自身抗体,它通过免疫介导反应可引起甲状腺滤胞细胞损伤,现有大量研究数据表明TPOAb的滴度随着硒的含量的变化而波动,提示硒的含量与TPOAb的滴度密切相关,进而影响甲状腺疾病的发生。