Predictive and sensitive biomarkers for thyroid dysfunctions during treatment with immune‐checkpoint inhibitors

Immune‐related adverse events (irAEs) are often seen during immune‐checkpoint inhibitor (ICI) treatment of various malignancies. Endocrine irAEs including thyroid dysfunctions are the most common irAEs, but their biomarkers remain unclear. In order to identify individuals who are susceptible to thyroid irAE for earlier diagnosis and appropriate follow‐up, the current study is aimed to investigate biomarkers of thyroid irAE. Herein, patients with advanced malignant diseases who received ICIs treatment were prospectively studied. Clinical and laboratory examination, thyroid function, and autoantibodies were evaluated at baseline, and every 4 wk after first treatment with ICIs. Cytokines/chemokines were measured at baseline and at 4 wk. In vivo effects of ICIs on experimental autoimmune thyroiditis were evaluated. Twenty‐six patients with malignant diseases who received ICIs treatment were enrolled in the study. Patients were divided into two groups: those who developed thyroid irAE, and those without irAEs. Comparing the two groups, early increase (≤4 wk) in serum thyroglobulin (Tg) levels and thyroid autoantibodies was seen in thyroid irAE (P < .05). Notably, higher levels of serum IL‐1β, IL‐2, and GM‐CSF at baseline, and early decrease of IL‐8, G‐CSF, and MCP‐1 were significantly associated in the development of thyroid irAE (P < .05). In vivo effects of anti‐PD‐1 antibody on deterioration of mice experimental thyroiditis were seen. In conclusion, early change in Tg, thyroid autoimmunity, and cytokine levels might indicate development of thyroid irAE. Pre‐existing thyroid autoimmunity might be involved with the development of thyroid irAE. Potential application of these factors as surrogate biomarkers for tumor therapy was indicated.     

Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis

Autoimmune associations in myasthenia gravis (MG)-patients and their relatives have not been re-assessed since their separation into early- or late-onset MG (EOMG, LOMG), or thymoma-associated MG.     

白癜风患者血清免疫球蛋白、补体、自身抗体检测及分析

目的 检测白癜风患者血清中免疫球蛋白IgG、IgA、IgM,补体C3、C4,抗核抗体(ANA)、抗甲状腺过氧化物酶抗体(A-TPO)、抗甲状腺球蛋白抗体(A-TG)的水平并进行比较分析.方法 收集门诊确诊为白癜风的患者血清168例和正常体检人群血清88例,性别、年龄分布无统计学差异,采用速率散射比浊法检测白免疫球蛋白IgG、IgA、IgM和补体C3、C4,采用ELISA法检测抗核抗体,采用电化学发光免疫分析法检测A-TPO、A-TG,结果用SPSS19.0统计软件进行分析.结果 白癜风患者组血清中免疫球蛋白IgG、IgA、IgM,补体C3、C4表达水平与正常人对照组差异不具有统计学意义(P＞0.05);白癜风组与正常对照组ANA阳性率分别为8.1％和5.7％,经比较差异不具有统计学意义(P＞0.05);两组间A-TPO的阳性率分别为18.8％和10.2％,差异有统计学意义(P＜0.05);两组A-TG阳性率分别为25.8％和4.5％,经比较差异具有统计学意义(P＜0.01).结论 部分白癜风患者存在体液免疫紊乱,在发病机制上可能与自身免疫性甲状腺疾病有相似之处;免疫球蛋白、补体及抗核抗体等免疫指标的检测在白癜风诊治中评价的意义不大.     

Effect of exogenous thyroid-stimulating hormone on thyroid papillary carcinoma cells in tissue culture

BACKGROUND: To determine the prognostic value of thyroid suppression therapy in patients with thyroid carcinoma, we studied the effect of thyroid-stimulating hormone (TSH) on the morphology, proliferation rate, and the T3, T4 production rate of primary thyroid carcinoma cells in culture. METHODS: From August 1997 to February 1998 tissues were collected for immediate culture from 13 patients undergoing surgery for thyroid cancer. Cells were incubated for 48 h with TSH in different concentrations. T3 and T4 production was measured by radioimmunoassay; cell proliferation was measured in a radioactive counter. Morphology was determined by cytologic examination. RESULTS: Ten samples were eligible for analysis. Changes in TSH affected T3 and T4 levels. The proliferation rate was not influenced by TSH levels. CONCLUSIONS: Thyroid papillary carcinoma cells grown in culture maintain their T3 and T4 synthesis ability. This ability is TSH-dependent and correlates with TSH concentration. The morphology of the cells is also maintained. However, their proliferation is not TSH-dependent, placing the current postthyroidectomy treatment policy in question.     

甲状腺癌~(131)I显像假阳性的分析及鉴别诊断

:1 3 1 　 I显像是诊断分化型甲状腺转移癌的特异方法 ,有关报道显示该方法诊断甲状腺转移癌的特异性为 96 % ,灵敏度为 80 %。但近年来也有不少报道指出假阳性结果的存在 ,如额窦粘液囊肿、胸腺、肺癌、乳房、食道良性狭窄、结肠移植物、胃上移、肾囊肿等均可见有 1 3 1　 I的蓄积 ,尽管其发生率不高 ,但常干扰诊断 ,导致病员接受不必要的照射。因此 ,对假阳性结果的出现部位 ,产生原因及可能的鉴别方法应该有所了解。为了得到正确诊断 ,可合并应用其他影像诊断方法 ,或辅以 2 0 1　 Tl显像 ,或辅以测定血中人甲状腺球蛋白 ( h- TG) ,以利于用药     

Conformational change of the thyroglobulin molecule induced by oxidation in vitro

Previous election-microscopical studies from this laboratory have shown that the thyroglobulin molecule can occur in two different conformations, one ovoid and the other cylindrical. Ovoid molecules are characteristic of well-iodinated thyroglobulin whereas cylindrical molecules are found after low-iodine diet or blocking of iodination. The present study was performed in order to elucidate the possible relation between the molecule conformation and the peroxidase-catalyzed reactions that occur in the thyroid in connection with hormone synthesis.Cylindrical thyroglobulin molecules (from PTU-exposed thyroids) were incubated in different media and the proportion of cylindrical and ovoid molecules after incubation was estimated in electron micrographs. It was found that incubation with glucose-glucose oxidase caused an extensive conversion of cylindrical molecules into ovoid molecules. Peroxidase and/or iodide were not necessary for this change of conformation. It is suggested that this in vitro molecule transformation was the result of an oxidation reaction.     

Models of in vitro thyroglobulin iodination

Currently available data on the mechanisms of chemical iodination of thyroglobulin (Van Zyl and Edelhoch, 1967; Lamas et al., 1970; Rolland et al., 1972) give the numbers of tyrosyl residues MIT, DIT and T₄ in relation to the quantity of iodine added to the incubating medium. Assuming that the chemical reactions are irreversible and that the duration of the experiment is sufficiently long for the reactions to be complete the experimental curves entail the definition of a minimum number of compartments.The classic model used by De Groot et al. (1971) has been simulated. It proves to be incompatible with the experimental data. A new model is required, according to which thyroglobulin would comprise tyrosine residues capable of binding one iodine atom (MIT) and tyrosine residues capable of binding two atoms of iodine (DIT); among these molecules only a certain fraction can couple to form triiodothyronine (T₃) and tetraiodothyronine or thyroxin (T₄). Three such models compatible with these biochemical constraints, have been simulated on the computer. The values of the reaction coefficients were chosen arbitrarily due to the absence of information on chemical iodination kinetics.The models agree with the data on in vitro iodination of thyroglobulin in an acellular medium.The models are used to propose experimental protocols enabling to test different hypotheses on thyroid hormone synthesis.     

Significance of postoperative serum thyroglobulin levels in patients with papillary and follicular thyroid carcinomas

BACKGROUND AND OBJECTIVES: Although there are many factors that affect postoperative serum levels of thyroglobulin (Tg), such levels have been previously used to detect recurrence of papillary and follicular thyroid carcinomas. This study was conducted to elucidate the significance of postoperative levels of Tg in patients with clinical presentations of papillary thyroid carcinoma, follicular thyroid carcinomas, or both. METHODS: To collect data pertaining to patients with thyroid cancer who were treated in Chang Gung Medical Center in Linkou, Taiwan, records relating to a total of 847 patients with pathologically verified papillary or follicular thyroid cancer, all of whom received total thyroidectomy and thyroid remnant ablation with radioactive iodide ((131)I), were studied. To evaluate the clinical significance of postoperative levels of Tg, the patients were categorized into three groups based on postoperative Tg level. Group A was classified as those demonstrating a 1-month postoperative Tg levels less than 1 ng/ml. Group B patients were classified as those displaying a 1-month postoperative Tg levels greater than or equal to 1 ng/ml, but less than 10 ng/ml. Group C patients were classified as those exhibiting a 1-month postoperative Tg levels great than or equal to 10 ng/ml. RESULTS: Of the patients in group A, none presented with distant metastases at the time of diagnosis or during the follow-up period. In group B, 15 patients (3.5%) died of thyroid cancer. In this group, tumor size was an important factor in cancer-related mortality, diagnostic clinical class, and follow-up status. Of the 491 patients in group C, 49 (10.0%) patients died of thyroid cancer. Among the patients in group C, age, histopathologic type, stage of diagnosis, and follow-up Tg values were important factors. Among groups A, B, and C, there were 161 (95.8%), 253 (76.4%), and 129 (37.1%) patients, respectively, with disease-free status at the end of 1998. CONCLUSIONS: Postoperative serum Tg levels can be used as a prognostic indicator in patients with papillary and follicular thyroid cancer. For patients with Tg levels greater than or equal to 10 ng/ml, Tg levels are a useful marker to predict prognosis.     

孕妇甲状腺球蛋白水平检测在碘缺乏病预防中的价值研究

目的 :探讨孕妇甲状腺球蛋白 (TG)水平和促甲状腺素 (TSH)水平之间的关系。方法 :应用免疫放射分析(IRMA)法检测了 10 0例碘缺乏地区孕妇的 TG和 TSH水平 ,并选择 10 0例非缺碘地区孕妇作为对照。结果 :研究组孕妇 TG均值为 17.6 ng/ m L± 4.6 7ng/ m L,对照组为 14.45 ng/ m L± 4.43ng/ m L(P<0 .0 5 )。研究组孕妇 TSH均值为 5 .36 m U / L± 2 .2 0 m U / L ,对照组为 4.6 9m U / L± 1.34 m U / L (P<0 .0 5 )。两组孕妇 TG水平和其 TSH水平呈显著正相关。结论 :孕妇的 TG水平可作为妊娠期预防碘缺乏的监测指标