Prevalence and clinical relevance of thyroid stimulating hormone receptor‐blocking antibodies in autoimmune thyroid disease

The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut‐off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb. In contrast, the prevalence of TBAb‐positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb‐positive patients, thirty‐nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively. Ten patients were both TBAb‐ and TSAb‐positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid‐associated orbitopathy was present in four of 82 (4·9%) TBAb‐positive patients, with dual TSHR antibody positivity being observed in three. TBAb correlated positively with TBII (r = 0·67, P < 0·001) and negatively with TSAb (r = –0·86, P < 0·05). The percentage of TBII‐positive patients was higher the higher the level of inhibition in the TBAb assay. Of the TBAb‐positive samples with  > 70% inhibition, 87% were TBII‐positive. Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism.     

Incidental langerhans cell histiocytosis of thyroid: case report and review of the literature

We report a case of a 42-yr-old woman with Langerhans cell histiocytosis (LCH) confined to the thyroid and associated with lymphocytic thyroiditis and a papillary microcarcinoma. This patient remains free of symptoms 14 mo after surgery. Thyroid LCH is rare. In children, it usually occurs as part of a multisystemic disease, whereas it is usually exclusive in adults. Isolated thyroid LCH is frequently associated with another thyroid disease, especially lymphocytic thyroiditis, suggesting that it is a reactive process rather than a neoplastic proliferation. The prognosis of isolated thyroid LCH is good. However, because it can rarely precede or reveal a multisystemic disease, additional investigations as well as a prolonged follow-up are justified.     

Human thyroglobulin peptide p2340 induces autoimmune thyroiditis in HLA-DR3 transgenic mice

In a previous study we demonstrated that the human thyroglobulin (hTg) peptide p2340 (aa 2340-2359) can stimulate a T cell response and elicit experimental autoimmune thyroiditis (EAT) in AKR/J (H-2(k)) mice. In the present study we examined whether p2340 can induce EAT in single HLA class II DR3 transgenic mice. This peptide was found to be immunogenic at the T cell level in DR3 mice, since it induced specific proliferative responses, as well as IL-2 and IFN-gamma secretion in secondary cultures of peptide-primed lymph node cells (LNC). Immunization of HLA-DR3 mice with p2340 in CFA elicited EAT (infiltration index of 1 to 2) in eight of nine mice. Peptide-primed LNC responded to intact hTg, whereas, hTg-primed LNC did not respond to p2340 in culture, suggesting that p2340 contains subdominant T cell epitope(s). P2340 was also found to be immunogenic at the B cell level, since strong p2340-specific IgG response was detected in all transgenic mice tested. Thus, we provide evidence for a pathogenic role of an hTg peptide in HLA-DR3 transgenic mice. Therefore, p2340 could be presented by DR3 molecule in patients with Hashimoto's thyroiditis and participate in the development of the disease.     

桥本氏甲状腺炎患者年龄、性别分布及自身免疫抗体水平分析

目的:分析桥本氏甲状腺炎(HT)在不同年龄男女性患者分布差异及相关抗体水平变化特点。方法:2014-01-01—2018-12-31五年间本院收治的HT患者共2705例,先按年龄分为儿童组(n=32)、青春期组(n=135)和成人组(n=2538),再将成人组中女性分为≤50岁组(n=1645)及>50岁组(n=519)两组,比较不同年龄组HT男女性占比差异,分析不同年龄组以及50岁前后女性甲状腺过氧化物酶抗体(TPOAb)和甲状腺球蛋白抗体(TgAb)的水平变化。结果:在三年龄组中,HT总病例数以成人组最多,儿童组较少。各年龄组间男性、女性HT占比差异有统计学意义(P<0.01);各年龄组内女性占比均显著高于男性,尤以成人组女性占比最高(P<0.01)。三年龄组间TPOAb、TgAb水平有显著统计学意义(均P<0.01)。青春期组及成人组TPOAb水平均低于儿童组(P<0.01),成人组与青春期组TPOAb水平差异无统计学意义(P>0.05);青春期组TgAb水平低于儿童组(P<0.01),儿童组与成人组间、青春期组与成人组间TgAb水平的差异均无统计学意义(P>0.05)。≤50岁与>50岁女性的TPOAb和TgAb水平比较均无统计学差异(P>0.05)。结论:成年人(>18岁)HT明显多于非成年人,且女性占比显著高于男性。TPOAb下降可能是成人HT的内分泌影响因素之一。     

Therapeutic effect of mesenchymal stem cell on Hashimoto’s thyroiditis in a rat model by modulating Th17/Treg cell balance

Abstract

The autoimmune condition Hashimoto’s thyroiditis (HT) is a disease wherein lymphocytes mediate the autoimmune damage and destruction of the thyroid gland. There are currently no effective means of treating HT, with the primary strategies of thyroid hormone therapy, surgery, or immunomodulatory therapy being associated with serious risks and side effects. There is thus a clear and urgent need to identify novel treatments for HT. In this study, we utilize female SD rats induced HT to evaluated the ability of transplanted MSCs to regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. The results showed that Rats in the HT model group exhibited increased thyroid autoantibody levels consistent with successful model development, whereas these levels were lower in rats treated with MSCs. There were also fewer thyroid lesions and less lymphoid infiltration of the thyroid in MSC-treated rats relative to HT model rats, as well as fewer Th17 cells and more Treg cells – an observation consistent with the cytokine analyses. All of these showed that MSCs can regulate Th17/Treg interactions in a rat Hashimoto’s thyroiditis (HT) model system. It suggested that transplanted MSCs could be a potential immunotherapy strategy for the treatment of Hashimoto’s thyroiditis.     

Thyroglobulin polymorphisms in Tunisian patients with autoimmune thyroid diseases (AITD)

The thyroglobulin (Tg) gene was reported to be linked and/or associated to autoimmune thyroid diseases (AITD) development in European Caucasian populations. Here, we attempt to replicate this finding and to evaluate the contribution of the Tg gene in the genetic susceptibility of AITD in the Tunisian population. We examined the genomic region (11.5cM) containing the Tg gene by genotyping seven microsatellite markers and four SNPs located respectively at exon 10 (Ser715Ala), exon 12 (Met1009Val), exon 21 (Ala1483Ala) and exon 33 (Arg1980Trp) in 15 Tunisian multiplex families affected with AITD including Graves' disease (GD) and Hashimoto's thyroiditis (HT) (members: 87; patients: 27 GD and 16 HT). A case-control study was performed by genotyping the Tgms2 intragenic microsatellite marker (intron 27) and four intragenic SNPs on 108 unrelated patients affected with GD and 169 normal controls. Analysis of family data did not show linkage of the thyroglobulin gene with AITD nor did analysis of case-control data show association of Tgms2 or SNPs with GD. In contrast to the European Caucasian population, we failed to detect any contribution of Tg gene in the genetic component of Tunisian AITD.     

Graves病和桥本甲状腺炎患者外周血T细胞表面及血清中Fas/FasL的表达特点

目的探讨Graves病(GD)和桥本甲状腺炎(HT)患者外周血中Fas+、FasL+细胞占总T淋巴细胞的比例(Fas%、FasL%)以及血清中sFas、sFasL、TGAb、TPOAb等指标的变化及意义。方法选择GD患者36例、HT患者32例、对照组20例。用流式细胞术检测外周血T细胞表面Fa(sCD95)、FasL(CD178)的表达特点,用双抗体夹心法(ELISA)测定血清中可溶性Fas及FasL的含量,用化学发光法测定相关抗体TGAb、TPOAb的含量。结果 GD及HT患者外周血Fas%均高于对照组(P<0.05),且以HT组更为显著,而各组均未检测到FasL的表达;GD及HT患者血清中sFas含量均高于对照组,尤以GD组显著;各组间均可检测到sFasL,但差异无统计学意义(P>0.05)。结论 Fas及其配体介导的凋亡在GD和HT的自身免疫反应过程中起着重要的作用。流式细胞术的应用,可为探讨AITD的发病机制提供新的方法。     

自身免疫性甲状腺炎腺体内淋巴细胞Fas-L的表达及血清sAPO-1/Fas测定的意义

为观察自身免疫性甲状腺炎（ＨＤ） 腺体内淋巴细胞Ｆａｓ－ Ｌ的表达及血清ｓＡＰＯ－ １／Ｆａｓ的测定, 与ＨＤ病因及临床意义的关联。本文应用抗链霉菌抗生素蛋白－ 过氧化酶连接法（ＳＰ法）对甲状腺细胞学涂片进行淋巴细胞Ｆａｓ－ Ｌ 的表达的观察; 并应用ＥＬＩＳＡ 法测定血清ｓＡＰＯ－ １／Ｆａｓ。结果表明, ＨＤ 腺体内淋巴细胞Ｆａｓ－ Ｌ的表达显著高于ＧＤ 组和对照组, Ｐ＜ ０ ．００１ ;血清ｓＡＰＯ－ １／Ｆａｓ 水平,ＨＤ低于ＧＤ、对照组和正常组,Ｐ＞ ０ ．０５ 。上述结果提示,ＨＤ腺体内淋巴细胞Ｆａｓ－ Ｌ表达的观察, 有助于评估ＨＤ治疗方法, 对治疗结果的影响,并对ＨＤ的发展和预后进行判断。     

硒对自身免疫性甲状腺炎大鼠甲状腺超微结构的影响

目的 观察硒干预后自身免疫性甲状腺炎(EAT)大鼠甲状腺超微结构改变,探讨硒对甲状腺自身免疫损伤反应的影响.方法建立自身免疫性甲状腺炎大鼠模型,对患病大鼠预防性和治疗性给予亚硒酸钠,观察其干预后甲状腺病理组织学变化和超微结构改变.结果实验结束时,硒预防EAT组和硒治疗EAT组TgAb、TmAb水平与EAT组相比明显下降(P＜0.05),且光镜下炎性细胞浸润明显减少,滤泡破坏减轻.电镜下EAT组大鼠主要表现为部分滤泡上皮细胞断裂,内质网高度扩张水肿,线粒体明显减少,部分线粒体嵴消失.硒预防组和硒治疗组均可见滤泡形态较规则,内质网扩张程度减轻,线粒体增多且结构趋于正常.结论 硒可预防和减轻自身免疫性甲状腺炎大鼠甲状腺的免疫性损伤.