过氧化物酶抗体诊断自身免疫甲状腺疾病临床价值的探讨

目的 通过比较自身免疫甲状腺疾病（ＡＴＤ）患者血清中过氧化物酶抗体（ＴＰＯ－Ａｂ）和甲状腺微粒体抗体（ＴＭＡｂ）水平，探讨测定ＴＰＯ－Ａｂ的临床价值。方法 采用放射免疫法同步测定２００例ＡＴＤ、５０例非ＡＴＤ、３０例健康对照血清中甲状腺过氧化物酶抗体和甲状腺微粒体抗体的浓度。结果 ①ＡＴＤ患者血清中ＴＰＯ－Ａｂ浓度显著升高（Ｐ〈０．０１）。②桥本甲状腺炎患者甲功的变化与体内ＴＰＯ－Ａｂ浓度有关，可     

人甲状腺过氧化物酶的纯化及与微粒体抗体的关系

用胆酸钠增溶、硫酸铵盐析、差速离心及免疫亲和层析法从甲状腺细胞膜成分中提纯ｈＴＰＯ，纯化ｈＴＰＯ的比生物活性提高了４３８．７倍，其ＲＺ值为０．２５．ＳＤＳ－ＰＡＧＥ于１０５ＫＤ和１０７ＫＤ处呈现两条条带。以固相Ｉｏｄｏｇｅｎ法标记ｈＴＰＯ，建立放免法测定２９例ＡＩＴＤ患者ＭｃＡｂ阳性血清的ＴＰＯＡｂ结合率为１６．３％±６．３％，而１１例正常人ＭｃＡｂ阳性血清的结合率为３．４％１４．７％，ＭｃＡｂ与ＴＰＯＡｂ结合率的测定值呈显著相关（ｒ＝０．７３，Ｐ＜０．００１）；稀释试验提示ＭｃＡｂ可与ｈＴＰＤ结合且存在剂量依赖性。因此ＡＩＴＤ患者的ＭｃＡｂ所针对的微粒体抗原即为ｈＴＰＯ，而ＭｃＡｂ即为ＴＰＯＡｂ。     

甲状腺过氧化物酶抗体对酶活性的影响

甲状腺过氧化物酶抗体对酶活性的影响王铸钢，等。中华内分泌代谢杂志１９９５；１１（３）：１３９观察ＴＰＯＡｂ阳性的ＡＩＴＤ血清与免疫亲和层析纯化的ＴＰＯ制剂反应后的酶活性变化。结果表明ＴＰＯＡｂ阳性血清（ｎ＝３２）与ＴＰＯ反应后酶活性较正常对照（ｎ＝３...     

自身免疫性甲状腺病TSH受体抗体异质性研究

目的 研究自身免疫性甲状腺病（ＡＩＴＤ）患者ＴＳＨ受体抗体（ＴＲＡｂ）的异质性。方法 选择异质性ＴＲＡｂ患者６例,用ＥＢ病毒转染其外周血Ｂ淋巴细胞并筛选能产一单克隆ＴＲＡｂ的阳性细胞孔。结果６例患者的ＴＳＨ结合抑制免疫球蛋白（ＴＢＨⅡ）测定值为５１￣８９％,患者１、２、４、５、６存在甲状腺兴奋性抗体（ＴＳＡｂ）,而患者１、２、３可测各甲状腺阻断抗性体（ＴＳＢＡｂ）、以ＥＢ病毒转染外周血Ｂ淋巴细胞后     

自身免疫性甲状腺疾病患者血中TSAb及TSBAb的观察

为了解自身免疫性甲状腺疾病患者体内刺激型及阻断型抗体共存情况，检测了４２７例Ｇｒａｖｅｓ病（Ｇｒａｖｅｓ′ｄｉｓｅａｓｅ，ＧＤ）及１０６例桥本甲状腺炎（Ｈａｓｈｉｍｏｔｏ′ｓｔｈｙｒｏｄｉｔｉｓ，ＨＴ）患者血中甲状腺刺激抗体（ＴＳＡｂ）及甲状腺刺激阻断抗体（ＴＳＢＡｂ），结果：ＧＤ组及ＨＴ组ＴＳＡｂ，ＴＳＢＡｂ的阳性率分别为９１．６％，７．７％及１４．２％，３７．７％，ＧＤ患者ＴＳＡｂ及ＴＳＢＡｂ     

710例甲状腺疾病自身抗体检测临床分析

７１０例甲状腺疾病自身抗体检测临床分析龚政石道中△甲状腺自身抗体检测是甲状腺疾病诊断手段之一。为正确认识甲状腺微粒体抗体（ＴＭＡｂ）及甲状腺球蛋白抗体（ＴＧＡｂ）的临床意义，本文对７１０例有完整资料的检测结果分析如下。１材料和方法１．１检测对象甲状腺...     

甲状腺刺激抗体作为Graves病预后指标的评价

以甲状腺刺激抗体（ＴｓＡｂ）及促甲状腺激素释放激素（ＴＲＨ）兴奋试验为指标，观察了５８例Ｇｒａｖｅｓ病（ＧＤ）患者抗甲状腺药物治疗前后ＴｓＡｂ变化及其作为评估ＧＤ预后的临床价值。结果显示：ＴｓＡｂ活性治疗前显著高于治疗后，经药物治疗后，ＴｓＡｂ明显下降或消失；停止治疗时，ＴｓＡｂ阳性或ＴＲＨ兴奋试验无反应者，ＧＤ复发率均为９３％；对复发组患者进一步分析后发现，停药时ＴｓＡｂ阳性率与ＴＲＨ兴奋试验不反应率分别为８４％和４５％，但二者间未能证实有相关关系；复发组平均治疗时间显著短于未复发组。以上结果表明，抗甲状腺药物具有一定的免疫抑制作用，反映ＧＤ免疫紊乱的ＴｓＡｂ用于估计预后时优于ＴＲＨ兴奋试验，治疗时间对复发与否有显著的影响。     

原发性甲状腺机能减退症患者血清甲状腺激素自身抗体放？…

目的：了解临床甲减病人血中甲状腺素自身抗体（Ｔ４Ａｂ）及３，５，３＇－三碘甲状腺原氨酸自身抗体（Ｔ３Ａｂ）分布状况。方法：采用放射免疫法测定１２０例原发性甲减患者的Ｔ３Ａｂ、Ｔ４Ａｂ。结果：甲减患者Ｔ３Ａｂ、Ｔ４Ａｂ的测定值分别为９．４２±４．４３％及１０．７３±４．６７％，较正常组升高非常显著（ｎ＝１２０，Ｐ〈０．０１）；其Ｔ３Ａｂ、Ｔ４Ａｂ的阳性率分别为３７．５０％及４０．８３％。对甲减分组，     

1961例甲状腺疾病患者血清TGA、TMA RIA结果分析

目的：放射免疫测定（ＲＩＡ）甲状腺球蛋白抗体（ＴＧＡ）、甲状腺微粒体抗体（ＴＭＡ）在甲状腺疾病诊断中的价值。方法：对１９６１例甲状腺疾病患者进行血清ＴＧＡ、ＴＭＡＲＩＡ。结果：甲亢患者１１８８例，ＴＧＡ、ＴＭＡ阳性率分别为４９．０７％和４５９５％；甲减１９１例，阳性率分别为４３．４５％和３９．２％；亚急性甲状腺炎７６例，阳性率分别为３８．１５％和３９．４７％；甲状腺结节４６３例，阳性率均为８．２％；桥本氏病４３例，阳性率均为９７．９％。结论：ＴＧＡ、ＴＭＡＲＩＡ是甲状腺疾病筛选诊断的重要手段之一，是桥本氏病的重要诊断依据。目的：放射免疫测定（ＲＩＡ）甲状腺球蛋白抗体（ＴＧＡ）、甲状腺微粒体抗体（ＴＭＡ）在甲状腺疾病诊断中的价值。方法：对１９６１例甲状腺疾病患者进行血清ＴＧＡ、ＴＭＡＲＩＡ。结果：甲亢患者１１８８例，ＴＧＡ、ＴＭＡ阳性率分别为４９．０７％和４５９５％；甲减１９１例，阳性率分别为４３．４５％和３９．２％；亚急性甲状腺炎７６例，阳性率分别为３８．１５％和３９．４７％；甲状腺结节４６３例，阳性率均为８．２％；桥本氏病４３例，阳性率均为９７．９％。结论：ＴＧＡ、ＴＭＡＲＩＡ是甲状腺疾病筛选诊断的重     

甲状腺疾病患者TsAb的阳性率调查

甲状腺疾病患者ＴｓＡｂ的阳性率调查李廷赵克明王玉凤辜晓萍沈守祥＊（安丘市人民医院山东安丘２６２１００＊潍坊市人民医院）促甲状腺受体抗体（ＴＲＡｂ）包括阻断型抗体（ＴｓＢＡｂ）和刺激型抗体（ＴｓＡｂ）两种亚型，ＴｓＡｂ是Ｇｒａｖｅ＇ｓ病（ＧＤ）发病的主...     

促甲状腺激素、甲状腺球蛋白抗体对甲状腺结节良、恶性的评估

目的 分析促甲状腺激素和甲状腺球蛋白抗体对甲状腺结节良恶性的判断价值.方法 整群选取2012年1月—2015年3月经该院病理切片确诊的23例甲状腺恶性结节(恶性组)、25例甲状腺良性结节(良性组)及健康志愿者20例(对照组)作为研究对象. 记录和比较所有研究对象进行促甲状腺激素、甲状腺球蛋白抗体水平及异常比例. 结果 恶性组促甲状腺激素[(3.46±1.23)vs(2.35±1.08)]和甲状腺球蛋白抗体[(135.43±49.46)vs(83.62±28.69)]水平高于良性组,差异有统计学意义(P<0.05);但两组2指标定性比较差异无统计学意义(P>0.05). 结论 促甲状腺激素、甲状腺球蛋白抗体在甲状腺良、恶性结节的确存在差异,但不宜采用人体正常参考值作为分别甲状腺良、恶性结节的标准.     

扶正清瘿法对甲状腺球蛋白抗体和甲状腺过氧化物酶抗体的影响

目的 探讨扶正清瘿法对自身免疫性甲状腺疾病患者血清Tg-ab和Tpo-ab的影响。方法 选取96例血清Tg-ab和Tpo-ab增高的患者,分别以中医辨证施治(中医组),采用扶正清瘿法为主治疗,及中西医结合治疗(中西组)和单纯西医治疗(西医组),观察疗效结果。结果 3组患者症状和体征评分均较治疗前降低,差异有统计学意义(P＜0.01);中医组、中西组、西医组分别有45、39、12例抗体下降,有效率分别为88.89%、76.92%、50%。治疗前后,中医组血清Tg-ab和Tpo-ab明显下降(P＜0.05),中西组和西医组Tg-ab和Tpo-ab差异无统计学意义(P＞0.05)。结论 扶正清瘿法具有明显的改善自身免疫性甲状腺疾病的症状和体征,能有效地降低血清Tg-ab和Tpo-ab的水平,纠正和改善甲状腺的功能。     

分化型甲状腺癌患者血清抗甲状腺球蛋白抗体、甲状腺过氧化物酶抗体及甲状腺球蛋白联合检测的临床意义

目的 探讨分化型甲状腺癌患者血清抗甲状腺球蛋白抗体(TGAb)、甲状腺过氧化物酶抗体(TPOAb)及甲状腺球蛋白(TG)联合检测的临床意义.方法 选取2019年1月至2020年8月于本院住院治疗的甲状腺疾病患者60例作为观察组,根据病理检查结果分为观察1组(良性结节)和观察2组(分化型甲状腺癌),每组30例.另取同期健康体检者30名作为对照组.比较3组TGAb、TPOAb与TG水平,分析各项指标与联合检测诊断分化型甲状腺癌的准确度、灵敏度与特异度.结果 观察2组TGAb、TG水平均高于对照组与观察1组,观察组TGAb、TPOAb水平均高于对照组,差异均有统计学意义(P<0.05);TGAb、TPOAb与TG联合检测诊断分化型甲状腺癌的准确度为82.22％,灵敏度为73.33％,特异度86.67％,均高于单一指标检测,差异均有统计学意义(P<0.05).结论 TGAb、TPOAb与TG联合检测可有效诊断分化型甲状腺癌,为疾病的临床治疗提供参考.     

Characterization of thyroid function and antithyroid antibody tests among Saudis

Objective:

To determine the reference intervals for thyroid function tests and the prevalence of thyroid autoimmunity in the Saudi population.

Methods:

A cross-sectional prospective study was conducted in King Khalid University Hospital, Riyadh, Saudi Arabia from January to June 2013. History and physical examination were obtained. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by Electro-chemiluminescence Immunoassay system-assay. Anti-thyroperoxidase, and anti-thyroglobulin antibodies were measured using enzyme-linked immunosorbent-assay. Subjects with previous or a family history of thyroid disorders, those taking medications affecting thyroid function, pregnant or lactating women, and those with goiter were excluded. Individuals with positive antibodies were excluded from the final analysis of the TSH reference range, but were used to determine the prevalence of thyroid autoimmunity.

Results:

Out of 337 Saudi subjects initially screened, 132 (aged 13-60 years) were candidates for reference calculation, the mean±standard deviation, and (2.5th-97.5th) percentile of TSH (mIU/L) was 1.96±0.9 (0.59-4.37), for FT4 (pmol/L) was 15.47±1.83 (12.04-19.13), and for FT3 (pmol/L) was 5.22±0.7 (4.07-6.76). The TSH was higher in the antibodies positive group (2.5±1.17 mIU/L) compared with the negative one (1.96±0.9 mIU/L) (p<0.05). Finally, 26% of subjects were tested positive for antithyroid antibodies.

Conclusion:

The TSH reference range was similar to laboratory references. Thyroid antibodies were prevalent in Saudis, necessitating further work in larger scale studies.Abnormalities of the thyroid gland are known to affect a considerable portion of the population worldwide. Precise diagnosis mandates accurate testing for thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), commonly known as thyroid function tests, and in some cases an evaluation of thyroid antibodies titer. These tests have to be interpreted while keeping in mind the population specific reference range.1 In adult Saudis, there is a lack of previous studies conducted to define the reference range of thyroid function tests. Furthermore, the prevalence of antithyroid antibodies among the adult Saudi population has not been estimated. Thyroid-stimulating hormone is the most sensitive test for the diagnosis of primary hypothyroidism. Debate over the definition of the upper limit of TSH calls for the establishment of a reference range among the adult Saudi population. Several factors result in variable TSH levels, such as ethnicity,1 geographic location,2 and specificity, and sensitivity of laboratory tests.3 For example, the National Academy of Clinical Biochemistry (NACB) has proposed lowering the upper limit to 2.5 mIU/L4 based on the 20-year cohort Whickham study,5 which found that subjects with serum TSH level >2 mIU/L at initial evaluation had an increased odds ratio for developing hypothyroidism, especially if thyroid antibodies were elevated.5 Furthermore, the American Association of Endocrinologists stated that although a TSH level between 3.0-5.0 uU/ml is within the normal range, it should be considered a sign of evolving thyroid underactivity.6 Additionally, the presence of thyroid antibodies, which is the main pathological determinant of progression to hypothyroidism, has not been estimated in our local population. In a study conducted on Saudi children,7 the prevalence of antithyroid antibodies was estimated to be 14%; however, this was an old study conducted in the pediatric age group. In the USA, for example, the prevalence among adults was estimated to be 10%.1 In view of the lack of studies measuring normal values for thyroid function tests, we aimed to determine the normal ranges of TSH, FT4, and FT3, and predict the prevalence of antithyroid antibodies in a Saudi adult population living in the Riyadh area.     

孕妇血TPOAb异常对妊娠结局的影响

目的通过对孕妇甲状腺过氧化物酶抗体(TPOAb)的测定,分析其阳性对孕早期甲状腺功能正常的孕妇妊娠结局的影响。方法以甲状腺功能正常的孕早期妇女为研究对象,比较TPOAb阳性和阴性组孕妇在妊娠过程中促甲状腺激素(TSH)水平,孕妇产科并发症的发生率和产后新生儿临床特征及TSH指标。结果在226例孕早期妇女中,TPOAb阳性和阴性组TSH水平差异有统计学意义(P<0.05);2组产科并发症的发生差异有统计学意义(P<0.05);新生儿身高、体重及Apagar评分等临床特征差异无统计学意义(P>0.05);但TPOAb阳性组产妇的新生儿TSH水平高于阴性组产妇的新生儿TSH水平,差异有统计学意义(P<0.05);相关分析显示,孕妇TPOAb滴度和TSH水平分别与新生儿TSH水平呈正相关(P<0.01)。结论 TPOAb阳性孕妇甲状腺功能有向亚临床甲状腺功能减退发展的趋势;孕早期妇女TPOAb阳性预示对其妊娠结局会有不利影响,孕妇TPOAb阳性可能会对新生儿甲状腺功能造成一定影响。     

人源甲状腺髓样癌噬菌体抗体库的构建及初步鉴定

目的：应用噬菌体抗体展示技术,构建大容量天然人源甲状腺髓样癌（medullary thyroid carcinoma,MTC）噬菌体单链抗体库。方法：提取ＭＴＣ病人癌周淋巴结总RNA,通过RT-PCR方法获得抗体可变区基因VH和VL基因片断,以它们为模板分别扩增VH-Linker和VL-Linker,再用剪切重叠延伸ＰＣＲ技术将之拼接组装成单链抗体可变区基因片段（single chain fragment variable,scFv）后引入酶切位点SfiⅠ和NotⅠ。将scFv基因克隆入噬菌粒栽体pCANTAB-5E后经电转入大肠杆菌Ecoli TG1,之后经辅助噬菌体M13K07超感染,构建人源MTC噬菌体单链抗体库。PCR鉴定scFv片段阳性插入率,1.0%琼脂糖凝胶电泳鉴定阳性克隆双酶切产物。结果：MTC周围淋巴结总RNA的琼脂糖电泳结果可见清晰的28 S、18 S条带;VH基因的大小约为370 bp,VL基因为350 bp,组装后的scFv基因约为750 bp。用pUC19标准质粒测定转化效率达到108 cfu/μg,scFv的阳性插入率为87.5％（21/24）。结论：成功地构建了人源MTC噬菌体展示文库,为进一步筛选具有MTC细胞特异性的人源噬菌体单链抗体奠定了实验基础。     

Prevalence of antithyroid microsomal antibody in thyroid patients of endemic goitre area

The region of greater Mymensingh known for iodine endemicity, recently came under iodine supplementation as a result of mandatory universal iodination of salt program. Autoimmune thyroid diseases (AITD) are among the most common human autoimmune disorders & presence of autoantibodies to the microsomal antigen (AntiMCAb) is a hallmark of disease activity. Both iodine deficiency & iodine supplementation precipitate increase rate of autoimmunity to the thyroid gland. Study was undertaken to determine prevalence of AntiMCAb positive cases among patients with various thyroid diseases. High resolution ultrasound (HRUS), serum thyroid hormone assays & scintiscan were used to classify the thyroid patients into 8 categories. 221 patients were studied during the stipulated period of 3 months. Male patients were 60 & female patients were 161. Age ranged from 11 to 65 years with median age 29.4 years. AntiMCAb test were done with radioimmunoassay (RIA). 126 patients had antimicrosomal antibody (57.01%). All form of hypothyroid (atrophic, goitrous, Hashimoto's) have very high rate of AntiMCAb positive cases. Highest 89.28% were seen in patients showing feature of Hashimoto's thyroiditis or generalized feature of AITD in HRUS with hypothyroidism, followed had 61.29% positive cases, However, antithyroid antibody was found in all form of thyroid disorders. Nodular goiter had 21.73% antiMCAb positive cases. AntiMCAb found positive at the rate of 33.33% in euthyroid patients with HRUS feature of AITD & diffuse euthyroid goiter, 40% in subclinical hypothyroid, 40% in subclinical hyperthyroid. Female rated higher in range of antimicrosomal antibody positivism. 59% of all thyroid patients among female subjects were AntMCAb positive, where as 51.67% male thyroid patients were positive. Highest number of positive cases found in the 30-35 age group. No definite pattern, however, was observed among age distribution. 20 age matched sample from patients unsuspected of thyroid disease shows 10% AntiMCAb positive compared to 73.33% of the same among same age group of thyroid patients. Frank Hashimoto's thyroiditis with positive antiMCAb and hypothyroidism were all detected by HRUS.     

甲状腺激素及抗体表达水平与糖尿病周围神经病变的相关性分析

目的 探讨甲状腺激素及抗体表达水平与糖尿病周围神经病变（diabetic peripheral neuropathy,DPN）的相关性。方法 选取2021年1月至2022年2月绍兴市人民医院肌电图室就诊的糖尿病患者186例,按照合并DPN的情况分为DPN组（n=68）和non-DPN组（n=118）。比较两组患者的身高、体质量、体质量指数（body mass index,BMI）、糖化血红蛋白（glycosylated hemoglobin,HbA1c）、游离三碘甲状腺原氨酸（free triiodothyronine,FT3）、游离甲状腺素（free thyroxine,FT4）、促甲状腺激素（thyroid-stimulating hormone,TSH）、甲状腺球蛋白抗体（thyroglobulin antibody,TGAb）、甲状腺过氧化物酶抗体（thyroid peroxidase autoantibody,TPOAb）,以及患者的年龄、糖尿病病程、糖尿病慢性并发症情况。结果 与NDPN组比较,DPN组患者年龄更大、DM病程更长,高血压患病率、糖尿病慢性并发症比例更高,FT3水平更低,差异均有统计学意义(P<0.05)。Spearman相关性分析显示,患者年龄、糖尿病病程、高血压及糖尿病慢性并发症与DPN呈正相关（P<0.05）,FT3与DPN呈负相关（P<0.05）。Logistic回归分析结果显示,糖尿病病程、FT3是DPN的影响因素（P<0.05）。结论 糖尿病患者积极监测FT3的变化或可为DPN的预测提供参考,积极控制甲状腺疾病,使甲状腺功能恢复正常,这或许能够保护周围神经,延缓糖尿病周围神经病变的发生和发展。     

Glycosylation of recombinant human thyroid peroxidase ectodomain of insect cell origin has little effect on recognition by serum thyroid peroxidase antibody

Background Thyroid peroxidase (TPO) is an important autoantigen in Hashimoto’s thyroiditis (HT), and almost all epitopes are located in TPO ectodomain. The glycosylation of TPO might contribute to breaking self-tolerance, therefore, purified glycosylated recombinant TPO ectodomain is prerequisite of elucidating its role in the pathogenesis of HT. The aim of our study was to investigate whether the glycosylation has influence on the antigenic determinants of recombinant TPO.

Methods Bac-to-Bac baculovirus expression system was used to generate recombinant human TPO ectodomain. The antigenicity was analyzed by antigen specific enzyme-linked immunosorbant assays (ELISAs). The glycosylation of recombinant human TPO ectodomain of High Five insect cell origin was detected by lectin-ELISAs.

Results TPO ectodomain was recovered from the culture media as a soluble protein, and it was fused with a hexahistidine tag which allowed purification by nickel-affinity chromatography. The recombinant TPO ectodomain could be recognized by all the 54 HT patients and three TPO monoclonal antibodies. Fucose, sialic acid and galactose were all detected on the recombinant TPO ectodomain. Sera TPOAb binding decreased slightly after non-specific deglycosylation of TPO by periodic acid.

Conclusions High Five insect cells derived recombinant human TPO ectodomain had N-glycosylation sites, which might have little effect on recognition by serum TPOAb.