Increase in antideoxyribonucleic acid antibody titer in postpartum aggravation of autoimmune thyroid disease

Serum antidouble stranded DNA antibody levels were measured during pregnancy and after delivery in women who had postpartum exacerbations of Graves' and Hashimoto's diseases. The changes in serum anti-DNA antibody levels closely paralleled those in the serum free T4 index, significantly increasing in the thyrotoxic phase 3-8 months postpartum in women with postpartum exacerbations of thyrotoxicosis due to Graves' disease and 1-3 months postpartum in women with postpartum destructive thyrotoxicosis of Graves' and Hashimoto's diseases. No change in anti-DNA antibody level was found in women with no postpartum exacerbations of thyroid diseases, nor could we demonstrate significant increases in serum anti-DNA antibody titers in patients with thyrotoxicosis due to subacute thyroiditis or in normal pregnant and postpartum women. The changes in serum anti-DNA antibody titers may reflect some generalized immunological abnormality in women who have postpartum exacerbations of Graves' or Hashimoto's diseases.     

Anti-thyroid peroxidase antibody in patients with autoimmune thyroid disease: possible identity with anti-microsomal antibody

Thyroid microsomal antigen and peroxidase (TPO) have a close intracellular anatomical relationship, especially in exocytotic vesicles. We considered that antibodies to microsomal antigen might react with TPO and therefore looked for the presence of antibodies against TPO in the serum of patients with autoimmune thyroid disease (AITD). TPO was prepared from Graves' thyroid glands, solubilized by n-octyl glucoside, and its activity was assayed by the guaiacol method. Control sera and sera with a positive microsomal hemagglutination test (MCHA(+) ) were assayed for their ability to precipitate TPO activity by incubation of sera with TPO and protein A. We identified MCHA(+) sera which caused precipitation of TPO activity, and the extent of precipitation was related to the amount of serum added. A significant correlation was present between this anti-peroxidase activity and microsomal antibodies titers, measured by a micro-ELISA method. Affinity columns prepared from immunoglobulins of MCHA(+) sera, coupled to Reacti-Gel (6X), bound TPO activity, whereas using control IgG the recovery in the unbound fraction was high. These data provide evidence of antibodies against thyroid peroxidase in the serum of patients with AITD and suggest a close link between microsomal antigen and thyroid peroxidase.     

Association of antipituitary antibody and type 2 iodothyronine deiodinase antibody in patients with autoimmune thyroid disease

Antipituitary antibody (APA) has been reported to be detected in patients with autoimmune thyroid disease. Type 2 iodothyronine deiodinase (D2) is expressed in both pituitary gland and thyroid gland. We studied the association of APA and D2 peptide antibody in patients with autoimmune thyroid disease. Rat pituitary gland homogenate and D2 peptide were used as antigens in the present study. APA and D2 peptide antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in sera obtained from 42 patients with Hashimoto's disease, 26 patients with Graves' disease and 70 healthy control subjects. Moreover, D2 activity precipitation assay was performed in some patients with Hashimoto's disease. APA and D2 peptide antibody were elevated in patients with Hashimoto's disease and patients with Graves' disease, compared with control subjects. APA was positive in 32.4% (22/68), D2 peptide antibody was positive in 26.5% (18/68) of patients with autoimmune thyroid disease. APA was positive in 31.0% (13/42) of patients with Hashimoto's disease and 34.6% (9/26) of patients with Graves' disease. D2 peptide antibody was positive in 26.2% (11/42) of patients with Hashimoto's disease and 26.9% (7/26) of patients with Graves' disease. D2 peptide antibody was correlated with APA in patients with autoimmune thyroid disease. Moreover, precipitation of D2 activity was increased in some patients with Hashimoto's disease including a patient who also had idiopathic diabetes insipidus, and was correlated with D2 peptide antibody. These results suggest that D2 antibody may be associated with APA in patients with autoimmune thyroid disease.     

甲状腺过氧化物酶抗体在自身免疫性甲状腺疾病中的表现

甲状腺功能亢进（甲亢）、甲状腺功能低下（甲低）和亚临床甲低患者甲状腺过氧化物酶抗体（TPOAb）、甲状腺球蛋白抗体（TGAb）和甲状腺微粒体抗体（TMAb）的阳性率和阳性患者的抗体水平均高于正常对照组，TPOAb阳性率在各组中又明显高于同组的TGAb和TMAb阳性率。甲状腺功能恢复正常的复诊组TPOAb阳性患者的抗体水平明显低于甲亢组、甲低组和亚临床甲低组。提示TPOAb对自身免疫性甲状腺疾病的诊断、治疗及预后评估具有一定的临床意义。     

Proteinuria in autoimmune thyroid disease

We have investigated the prevalence of proteinuria in patients with Graves' disease and chronic autoimmune thyroiditis attending a routine thyroid clinic. Using the urine protein creatinine index, proteinuria was found in 29.8% of patients with autoimmune thyroid disease and in 9.5% of patients attending the same clinic but without these conditions. When patients with Graves' disease were treated with 131I, proteinuria measured by 24 h collections developed in 9 of 14 patients without pre-existing proteinuria and appeared to diminish in 4 patients in whom proteinuria had been present before treatment. The prevalence and fluctuation of proteinuria was independent of thyroglobulin and microsomal antibody levels. We were unable to confirm previous reports of a high prevalence of circulating immune complexes in autoimmune thyroid disease; complexes were detected in only 7.9% of patients and did not correlate with proteinuria. The causes of mild proteinuria in autoimmune thyroid disease are not apparent, but previous case reports suggesting that membranous glomerulonephritis is associated with Graves' disease, albeit rarely, indicate that immunological mechanisms may be implicated.     

'Linkage analysis of thyroid antibody production: evidence for shared susceptibility to clinical autoimmune thyroid disease

Context: Epidemiological data suggest a genetic susceptibility to thyroid antibody (TAb) production. Objective: The objective of the study was to identify genetic loci that are linked with TAb production. Design: The design of the study was a whole genome linkage study in families with clustering of thyroid autoimmunity. Settings: The study took place at an academic medical center. Participants: Participants included 102 multigenerational families (540 individuals) multiplex for autoimmune thyroid disease (AITD) and TAb production. Main Outcome Measures: We computed two-point logarithm of odds (LOD) scores and multipoint heterogeneity LOD scores for 400 microsatellite markers spanning the entire human genome at an average distance of 10 cm ( approximately 10 Mb). Results: Three loci showed evidence for linkage with TAb production: 1) 2q locus, which gave a maximum multipoint heterogeneity LOD score (HLOD) of 2.8 and contained the CTLA-4 gene, previously reported to be linked and associated with clinical AITD; (2) 6p locus (HLOD 2.5), which was the same AITD-1 locus found to be linked with clinical AITD; and (3) 8q locus (HLOD 2.2), which contained the thyroglobulin gene, also previously reported to be linked and associated with AITD. All loci that were linked to TAb were also linked to AITD, suggesting that TAb and AITD share the same genetic predisposition. Conclusions: We conclude that: 1) some of the genes/loci predisposing to TAb and AITD are shared, whereas distinct genes/loci also exist; (2) the presence of TAb in relatives of AITD patients may be associated with increased risk for the development of clinical AITD; and (3) further studies are needed to determine the predictive value of TAb levels for the development of clinical AITD in relatives of patients with familial AITD.     

Non-thyroid autoantibodies in autoimmune thyroid disease

Autoimmune thyroid disease is frequently accompanied by other organ-specific and non-organ-specific diseases, most likely because there is sharing of genetic and possibly environmental susceptibility factors. These associations are well recognized in the autoimmune polyglandular syndromes; autoimmune thyroid disease is one of the three major endocrinopathies in the type 2 syndrome and occurs in around 4% of type 1 patients. This review considers the frequency of disease-specific autoantibodies in patients with thyroid autoimmunity and briefly examines the role of such antibodies in performing screening for the associated conditions. Recommendations are made for using such autoantibody tests in the setting of patients with autoimmune thyroid disorders, and also for the utility of screening for thyroid autoimmunity in patients with pernicious anaemia, Addison's disease, coeliac disease, primary biliary cirrhosis, myasthenia gravis, lymphocytic hypophysitis, systemic lupus erythematosus and rheumatoid arthritis. At present, however, there are no large-scale trials that have shown the cost-benefit ratio of autoantibody screening for autoimmunity screening, and clinicians must use individual judgement combined with heightened awareness to identify who to test.     

细胞因子与自身免疫性甲状腺疾病

自身免疫性甲状腺疾病(AITD)是最常见的器官特异性自身免疫性疾病,其中辅助性T细胞(Th)1/Th2细胞因子的动态平衡在维持正常的细胞免疫和体液免疫中起重要作用,一旦这种平衡被打破,将导致AITD的发生.这些细胞因子可以直接影响机体免疫细胞的活性,也可以通过影响甲状腺细胞免疫相关因子的表达,影响AITD的发生、发展,因此对细胞因子在AITD中发生机制的深入研究可为临床诊治提供更充分的理论依据.     

自噬与自身免疫性甲状腺疾病

自噬是细胞的一个重要生物学过程,它对维持细胞存活和自身稳态发挥重要作用.大量研究表明,自噬及其相关蛋白参与调控淋巴细胞发育和免疫应答,在多种自身免疫性疾病中发挥着重要的调控作用.近年研究发现,细胞自噬与自身免疫性甲状腺疾病的发生、发展密切相关,结合近几年自身免疫性甲状腺疾病与自噬相关的报道,对自噬形成过程中的分子调控机制、自噬与自身免疫性甲状腺疾病的关系进行综述.     

细胞因子与自身免疫性甲状腺疾病

自身免疫性甲状腺疾病(AITD)是最常见的器官特异性自身免疫性疾病,其中辅助性T细胞(Th)1/Th2细胞因子的动态平衡在维持正常的细胞免疫和体液免疫中起重要作用,一旦这种平衡被打破,将导致AITD的发生.这些细胞因子可以直接影响机体免疫细胞的活性,也可以通过影响甲状腺细胞免疫相关因子的表达,影响AITD的发生、发展,因此对细胞因子在AITD中发生机制的深入研究可为临床诊治提供更充分的理论依据.     

细胞因子与自身免疫性甲状腺疾病

自身免疫性甲状腺疾病(AITD)是最常见的器官特异性自身免疫性疾病,其中辅助性T细胞(Th)1/Th2细胞因子的动态平衡在维持正常的细胞免疫和体液免疫中起重要作用,一旦这种平衡被打破,将导致AITD的发生.这些细胞因子可以直接影响机体免疫细胞的活性,也可以通过影响甲状腺细胞免疫相关因子的表达,影响AITD的发生、发展,因此对细胞因子在AITD中发生机制的深入研究可为临床诊治提供更充分的理论依据.     

Pregnancy and autoimmune thyroid disease

Pregnancy has profound effects on the course of Graves' disease and Hashimoto's thyroiditis. Understanding of this interrelationship may clarify the role of the numerous immunologic gestational alterations that facilitate survival of the fetal allograft. Also, it should provide a more rational basis in the management of Graves' hyperthyroidism during pregnancy. Epidemiologic data indicate that screening for thyroid dysfunction appears justified in women in the postpartum period. The natural history of the postpartum thyroiditis syndrome remains to be fully evaluated, but the evidence indicates thyroid abnormalities can still be found in many patients several years after onset. Accordingly, the importance of follow-up cannot be overemphasized.     

Rheumatic manifestations of autoimmune thyroid disease: the other autoimmune disease

Autoimmune thyroid disease (AITD) is an inflammatory thyroiditis that in some cases is characterized by lymphocytic infiltration of the thyroid gland, also referred to as chronic lymphocytic thyroiditis or Hashimoto thyroiditis. Hashimoto thyroiditis is one of the commonest causes of hypothyroidism. Hypothyroidism has been associated with osteoarthritis (OA) and inflammatory forms of arthritis and with several well defined connective tissue diseases, which in turn can cause arthritis. The presence of arthritis in patients with AITD with normal thyroid function is now being increasingly recognized. There is also considerable evidence to suggest that AITD is highly associated with fibromyalgia syndrome. We review the current literature on the rheumatologic manifestations of AITD and describe the features in its presentation that set it apart from other forms of autoimmune arthritis.     

成人隐匿性自身免疫糖尿病与甲状腺自身免疫的关系

目的探讨成人隐匿性自身免疫糖尿病(LADA)与甲状腺自身免疫的关系.方法对90例LADA患者、104例1型糖尿病(T1DM)患者、100例2型糖尿病(T2DM)患者和100例健康对照进行甲状腺过氧化物酶抗体(TPO-Ab)、甲状腺球蛋白抗体(TG-Ab)检测.糖尿病患者还进行谷氨酸脱羧酶抗体(GAD-Ab)检测.TPO-Ab、TG-Ab采用放免法检测,GAD-Ab采用放射配体法检测.结果(1) LADA患者TPO-Ab的检出率为16.7%(15/90)高于T2DM患者(7.0%, 7/100; P<0.05).LADA患者中任一甲状腺自身抗体(TPO-Ab或 TG-Ab阳性)的检出率与T1DM差异无显著性(18.9%,17/90比25.0%,26/104,P>0.05),且均高于正常对照的8.0%(8/100, P<0.05).(2)携高滴度GAD-Ab(GAD-Ab指数≥0.5)的LADA患者中任一甲状腺自身抗体的检出率为50.0%(9/18),高于低滴度GAD-Ab 的LADA患者(12.5%, 8/64; P<0.05).(3) 甲状腺自身抗体阳性的LADA患者甲状腺功能异常率高于抗体阴性者(47.1 %, 8/17比17.1%, 6/34, P<0.05).结论 (1)LADA患者, 尤其是携高滴度GAD-Ab的 LADA患者,与经典的T1DM相似,易合并甲状腺自身免疫紊乱.(2)LADA患者甲状腺自身抗体的存在预示甲状腺功能异常的风险增高.(3)LADA可作为自身免疫多内分泌腺病综合征(APS)的一个重要组成成分,且常以APS-Ⅲ型存在.     

Anti-Saccaromyces Cerevisiae antibodies (ASCA) are elevated in autoimmune thyroid disease ASCA in autoimmune thyroid disease

Environmental factors have been implicated in the development of autoimmune thyroid disease (AITD). Anti-Saccaromyces Cerevisiae Antibodies (ASCA) were shown to be elevated in several autoimmune diseases. The aim of the study was to determine ASCA levels and their relationship with thyroid autoantibodies in patients with AITD. One-hundred and twelve patients with AITD (age 41.1±12.8 years; F/M:96/16) and 103 healthy controls (38.5±10.3 years; F/M:82/21) were included. Twenty-four patients had Graves disease (GD), and 88 had Hashimoto's thyroiditis (HT). ASCA IgA and IgG, TSH, free T4, anti-thyroglobulin, and anti-thyroid peroxidase antibody concentrations were determined. ASCA IgA positivity in patients with GD (16.6%) was similar to patients with HT (13.6%) and was higher than controls (5.8%). No significant difference was present between the frequencies of IgG positivity among GD (12.5%), HT (7.9%), and control groups (5.8%). The mean levels of ASCA IgA and IgG were comparable within the groups. No correlation of ASCA and anti-thyroglobulin and anti-thyroid peroxidase levels was observed. Increased IgA ASCA positivity is observed in patients with GD, suggesting a role of environmental stimuli in its pathogenesis. The role of ASCA in the etiology of AITD needs to be further examined.