Autoimmune Thyroid Diseases in Patients with Undifferentiated Connective Tissue Disease

Previous data have indicated that organ-specific and non-organ-specific autoimmune diseases may occur in the same patient. We report here our study on the type and prevalence of endocrine autoimmune diseases in undifferentiated connective tissue disease (UCTD). A retrospective analysis revealed five out of 75 UCTD cases (6.6%) with cytology-verified autoimmune thyroiditis (associated with insulin-dependent diabetes mellitus in one case). Other UCTD patients had Graves’ disease (one case), non-toxic multinodular goitre (two cases) and central hypothyroidism (one case). In a prospective study, thyroid function was evaluated in 15 consecutive UCTD patients with neither clinical nor laboratory signs of thyroid involvement. Basal and post-TRH stimulation TSH levels were significantly higher in UCTD patients than in healthy subjects. Received: 25 March 1999 / Accepted: 9 July 1999     

Gastric Mucosa-Associated Lymphoid Tissue in Autoimmune Thyroid Diseases

Background: There is increasing evidence for a link between Helicobacter pylori infection and the development of lymphoid follicles in the gastric mucosa. It is not known whether other factors may also play a role. The aim of this study was to investigate the role played by the host with peculiar immunogenic disorders, in the presence or absence of a known antigenic stimulus such as H. pylori For this, we studied patients with autoimmune thyroid diseases. Methods: Thirty patients with autoimmune thyroid diseases and 30 dyspeptic patients without a history of thyroid disorders (as control group) underwent upper endoscopy. Lymphoid follicles and H. pylori status were assessed by histopathologic and enzymatic analysis. Results: Organized mucosa-associated lymphoid tissue was found in 73.3% of the patients and in 33.3% of control group. Lymphoid follicles were found in 87.5% of the H. pylori-positive patients and in 57.1% of the H. pylori-negative patients (P = NS). In the control group these follicles were present in 50% of H. pylori-positive subjects and in 14.3% of those who were H. pylori-negative. Conclusions: Lymphoid follicles in the gastric mucosa are common in autoimmune thyroid diseases. Besides H. pylori infection, other factors (environmental, unknown infectious agents) or mechanisms related to the underlying disease may play a causal role.     

Clinical and Subclinical Autoimmune Thyroid Disease in Adult Celiac Disease

Our aim was to investigate the occurrence of clinical and subclinical autoimmune thyroid disease in 79 patients with celiac disease as reflected in thyroid function, antibodies, and ultrasound. Since subclinical thyroid diseases are common in the population, 184 nonceliac controls were also studied. Normal thyroid function combined with positive antibodies and marked hypoechogenicity was considered subclinical disease. Autoimmune thyroid disease was observed in 13.9% of celiac patients and in 2.1% of controls (P = 0.0005); and subclinical disease in 10.1% and 3.3%, respectively (P = 0.048). The mean thyroid gland volume was 8.3 ml in celiac patients and 10.4 ml in controls (P = 0.007). Hypoechogenicity was found in 73% of celiac patients and in 42% of controls (P < 0.0001). Positive thyroid antibodies were associated with hypoechogenicity in celiac patients but not in controls. In conclusion, the occurrence of both clinical and subclinical autoimmune thyroid disease was increased in celiac disease; subclinical thyroid disease indicates regular surveillance.     

Prevalence of Celiac Disease in Turkish Children with Autoimmune Thyroiditis

The close association between celiac disease (CD) and autoimmune disorders is well documented in adult and pediatric patients. The aim of this study is to determine the prevalence of CD in Turkish children with autoimmune thyroiditis (AT). Sera from 101 children with AT (11 boys and 90 girls, from 2 to 18 years of age; mean age 12.28 ± 3.26 years) and 103 healthy children (46 boys and 57 girls, from 3.5 to 17 years of age; mean age 12.18 ± 3.11 years) were screened for CD using the IgA anti-tissue transglutaminase (IgA anti-tTG) antibody and total serum IgA. Small intestinal biopsy was offered to all antibody-positive patients. IgA anti-tTG was positive in eight children (7.9%) with AT. None of the serum samples of healthy children were positive for IgA anti-tTG antibody. Selective IgA deficiency was not detected in patients or controls. Intestinal biopsy was accepted by seven patients. In five patients (4.9%), subtotal villous atrophy was found. These findings indicate that the prevalence of CD is higher in Turkish children with AT than in healthy controls. Routine screening for CD should be performed in children with AT.     

自身免疫性肝炎和原发性胆汁性肝硬化患者自身免疫性甲状腺疾病流行率调查*

目的 调查自身免疫性肝病(AILD)患者自身免疫性甲状腺疾病(AITD)发病率情况。 方法 2018年6月～2020年12月我院诊治的自身免疫性肝炎(AIH)41例和原发性胆汁性肝硬化(PBC)患者45例,采用间接免疫荧光法或免疫印迹法检测血清抗核抗体(ANA)、抗线粒体抗体(AMA)或AMA-M2)、抗平滑肌抗体(ASMA)、抗双链DNA抗体(抗dsDNA)和抗着丝点抗体(ACA);采用ELISA法检测血清免疫球蛋白,包括IgG、IgM和γ-球蛋白。结果 在本组41例AIH患者中,合并HT患者12例,合并GD患者6例,在45例PBC患者中,合并HT患者8例,合并GD患者7例;AIH患者血清IgG水平为17.5(14.8,19.8)g/L,显著低于AIH合并HT组【21.6(17.5,29.0)g/L,P<0.05】或AIH合并GD组【22.4(20.2,26.4)g/L,P<0.05】,血清γ-球蛋白为22.2(19.3,25.6)%,显著低于合并HT组【26.5(22.2,32.2)%,P<0.05】或合并GD组【27.1(24.3,32.0)%,P<0.05】;PBC患者年龄为(55.2±1.1)岁,显著小于合并HT组【(62.4±1.6)岁,P<0.05】或合并GD组【(62.2±1.5)岁,P<0.05】,血清IgG水平为15.4(12.2,18.0)g/L,显著低于合并HT组【20.3(16.8,24.7)g/L,P<0.05】或合并GD组【21.3(16.8,25.6)g/L,P<0.05】,血清γ-球蛋白水平为21.2(17.8,25.6)%,显著低于合并HT组【26.7(21.7,30.4)%,P<0.05】或合并GD组【25.4(22.2,29.4)%,P<0.05】。结论 AILD合并AITD的发病率较高,合并AITD患者血清IgG和γ-球蛋白水平较高,其原因还有待于进一步研究。     

结缔组织病与甲状腺疾病的相关性

目的探讨常见结缔组织病(connective tissue disease,CTD)与甲状腺疾病的相关性。方法以济宁医学院附属医院2009年1月至2013年4月住院并接受甲状腺功能筛查CTD患者为研究对象,以普通人群为对照,比较CTD患者与普通人群甲状腺疾病的患病率,同时比较不同甲状腺疾病在不同CTD中的患病率。结果 CTD患者780例,包括类风湿关节炎438例(56.2%)、系统性红斑狼疮195例(25.0%)、原发性干燥综合征85例(10.9%)、混合结缔组织病44例(5.6%)、系统性硬化症(SSc)18例(2.3%),其中合并甲状腺疾病286例(36.7%),与普通人群比较(8.7%)明显升高(P0.05)。合并甲状腺疾病的CTD患者,发生率依次为混合结缔组织病61.4%、原发性干燥综合征54.1%、系统性红斑狼疮51.3%、系统性硬化症27.8%、类风湿关节炎24.7%;混合结缔组织病、原发性干燥综合征、系统性红斑狼疮发生率与类风湿关节炎比较,差异有统计学意义(P0.05)。CTD患者合并甲状腺疾病构成比依次为甲状腺功能减退29.4%、甲状腺功能亢进6.3%、桥本甲状腺炎18.5%、低T3综合征26.6%、结节性甲状腺肿18.8%、甲状腺肿瘤0.4%。结论 CTD合并甲状腺疾病发生率较高,应重视两种疾病的相互筛查。     

血吸虫感染调节自身免疫性疾病和过敏性疾病的研究进展

血吸虫感染可下调Th1细胞介导的自身免疫性疾病和Th2细胞介导的过敏性疾病。新近研究发现,致病性CD4+T细胞亚群、Th17细胞也参与多种自身免疫等病理性疾病的发病,血吸虫感染也可下调自身免疫性疾病中的Th17细胞反应。本文综述了血吸虫感染下调自身免疫或过敏性疾病中Th1、Th2、Th17细胞的反应及其作用机制的研究进展。     

Shared Genetic Risk Factors in Autoimmune Liver Disease

To determine if shared genetic risk factors for autoimmune liver disease affect clinical manifestations, we evaluated 271 patients and 92 normal subjects by DNA-based techniques. Genetic risk factors were intermixed in all conditions, and frequency varied according to disease type. DR4 distinguished autoimmune hepatitis (P = 0.0002) and primary biliary cirrhosis (P = 0.004) from primary sclerosing cholangitis. DR52 distinguished primary sclerosing cholangitis from autoimmune hepatitis (P = 0.0007) and primary biliary cirrhosis (P = 0.00007) and DR3 distinguished autoimmune hepatitis (P = 0.002) and primary sclerosing cholangitis (P = 0.0005) from primary biliary cirrhosis. Only the occurrence of DR4 in primary sclerosing cholangitis was lower than in normal subjects (P = 0.02). Patients with mixed genetic risk factors did not have distinctive features or manifestations of hybrid conditions. We conclude that patients with shared genetic risk factors do not have characteristic features nor do they have overlap syndromes. DR4 may be protective against primary sclerosing cholangitis.     

信阳农村高血压人群外周动脉病发生率及影响因素

目的探讨高血压患者中外周动脉病的发生率和影响因素。方法在信阳农村7个社区对年龄40～75岁人口进行横断面调查,共筛查出高血压患者4716名,调查高血压人群中外周动脉病(踝臂指数≤0.9)的发生率及相关危险因素。结果在高血压患者中,外周动脉病的发生率为8.7%。与无外周动脉病者相比,外周动脉病患者年龄更大,传统心血管病危险因素更多,包括收缩压增高[(170.1±22.6)比(166.6±22.7)mm Hg,P<0.01)]、脉压增大,血糖增高[(5.8±2.2)比(5.6±1.7)mmol/L,P<0.05],总胆固醇增高[(5.7±1.3)比(5.5±1.1)mmol/L,P<0.05],血尿酸增高。多元Logistic回归调整了年龄、性别及其他心血管病危险因素后,与外周动脉病相关的因素为:吸烟史(OR=1.65,95%CI1.18～2.29),脑卒中病史(OR=1.50,95%CI1.12～2.00),高尿酸血症(OR=1.54,95%CI1.10～2.15),总胆固醇(OR=1.12,95%CI1.02～1.23)、体质量指数(OR=0.95,95%CI0.93～0.98)。结论信阳农村高血压患者外周动...     

Prevalence of Asthma and Other Childhood Allergies in Brazilian Schoolchildren

We determined the prevalence of asthma, rhinitis, and eczema among Brazilian children using the standardized protocol of the International Study on Asthma and Allergies in Childhood (ISAAC) to facilitate the comparison of our results with other studies using the ISAAC methodology. We conducted a cross-sectional study from June to October 1994 to determine the prevalence of asthma, rhinitis, and eczema in 5182 school children aged 7-8 years and 13-14 years residing in the Brazilian towns of Santa Maria and Itabira (iron-mining cities located in Minas Gerais). Parents completed questionnaires at their child's school in the presence of trained interviewers. The cumulative prevalence of doctor-diagnosed asthma was 4.6% for all ages with no significant difference between the age groups. In general, there was a higher prevalence of symptoms in the younger age group than the older. The prevalence of wheezing in the previous 12 months was 14.3% (7-8 years old) and 9.3% (13-14 years old) (p ≤ 0.01), of chronic cough in the previous 12 months was 25.6% (7-8 years old) and 22.1% (13-14 years old) (p ≤ 0.01), and of nighttime cough in the previous 12 months was 22.3% (7-8 years old) and 19.4% (13-14 years old) (p ≤ 0.05). Overall the prevalences of asthma and wheezing symptoms in the previous 12 months were higher for boys than girls (5.2% vs. 3.9% for asthma, p ≤ 0.01, and 13.2% vs. 10.6% for wheezing, p ≤ 0.01, respectively). These results suggest that asthma-related respiratory illnesses affect a substantial part of the childhood population in Itabira and Santa Maria, Minas Gerais. Some factors such as male gender and younger age may be associated with an increase risk for chronic respiratory symptoms. Prevalences of asthma and allergic diseases in these Brazilian cities on the basis of self-reporting of symptoms and of one's medical history may more accurately portray the true prevalence of asthma than the use of medical records.     

Pathogenesesis of Ophthalmopathy in Autoimmune Thyroid Disease

What causes GO is still a mystery, but the disease process results from a complex interplay of genetic and environmental factors. Genes such as those for HLA genes may determine a patient's susceptibility to the disease and its severity, but environmental factors, often unknown, may determine its course. Once established, the chronic inflammatory process within the orbital tissues appears to take on a momentum of its own. Given our current state of knowledge, the following working scheme for the pathogenesis of GO can be proposed (Fig. 1): On the background of a permissive immunogenetic milieu, circulating T cells in patients with GD, directed against certain antigens on thyroid follicular cells, recognize antigenic epitopes that are shared by tissues contained in the orbital space. Of the cell types residing in these tissues, preadipocytes and fibroblasts, most likely act as target and effector cells of the orbital immune process, respectively. This includes preadipocyte fibroblasts present in the perimysium of extraocular muscles, which do not appear to be immunologically different from those located in the orbital connective tissue. Orbital preadipocyte fibroblasts may be stimulated by unknown circulating or locally produced factors to differentiate into mature adipocytes that express increased levels of TSHr. How autoreactive T cells escape deletion and control by the immune system and come to be directed against a self-antigen presented by cells residing in the thyroid gland and extrathyroidal locations, is still unknown. Proliferation and expansion of autoreactive T cell clones may be due to mimicry of a host antigen by a microorganism, but this remains speculative. T cell recruitment into the orbital tissues is facilitated by certain chemokines and cytokines, which help to attract T cells by stimulating the expression of certain adhesion molecules (e.g., ICAM-1, VCAM-1, CD44) in vascular endothelium and connective tissue cells. These adhesion receptors are known to also play an important costimulatory role by activating T cells and facilitating antigen recognition, which amplifies the cellular immune process. Analysis of variable region genes of T cell antigen receptors in orbital T cells of patients with active GO has revealed their restricted TcR V gene usage, suggesting that antigen-driven selection and/or expansion of specific T cells may occur early in the evolution of GO. T cells and macrophages populating the orbital space are known to synthesize and release a [figure: see text] number of cytokines (most likely a Th1-type spectrum) into the surrounding tissue. Cytokines, oxygen free radicals and fibrogenic growth factors, released both from infiltrating inflammatory and residential cells, act upon orbital preadipocytes in a paracrine and autocrine manner to stimulate adipogenesis, fibroblast proliferation, glycosaminoglycan synthesis, and the expression of immunomodulatory molecules. Smoking, a well-known aggravating factor in GO, may aggravate tissue hypoxia and exert important immunomodulatory effects. The long held hypothesis of a thyroid cross-reactive antigen within the orbital tissues has recently gained significant support by an animal model of GO, and by in vitro and ex vivo studies. If confirmed in immunological studies, these data may well explain the localized infiltration of the orbital tissues by autoreactive lymphocytes that share intriguing molecular features with intrathyroidal lymphocytes. Local release of particular cytokines, TSHr-directed antibodies, or other factors might further enhance adipogenesis, glycosaminoglycan synthesis and expression of immunomodulatory proteins within the orbit. Other factors, including inflammatory cytokines, might act as counterbalancing inhibitors of these effects. However, if the net effect of these changes is to increase the volume of the fatty connective tissues within the orbit, then proptosis, extraocular muscle dysfunction, and periorbital congestion will ensue. Whether this hypothetical sequence of events will finally explain the involvement of the orbit in GD is unknown. Future studies will be aimed at identifying factors that might modulate adipogenesis in orbital cells and clarifying the link between adipogenesis and TSHr expression in the orbit. Taken together, a number of important details in the complex pathogenesis of GO have been resolved in recent years, but many challenges are still ahead. Elucidation of the primary antigen and how it is recognized by the immune system will be key issues.     

Association of Autoimmune Hepatitis and Cardiovascular Disease

BackgroundAutoimmune Hepatitis is a chronic liver disease while Cardiovascular Disease is seen in inflammatory states. This study sought to determine if Cardiovascular Disease was associated with Autoimmune Hepatitis.MethodsThe National Inpatient Sample selected patients with a primary diagnosis of Autoimmune Hepatitis and secondary diagnosis of Cardiovascular Disease in 2014. The primary outcome was the association of Autoimmune Hepatitis with Cardiovascular Disease. Secondary outcomes evaluated the hospital burden with Cardiovascular Disease.Results16,375 patients with Autoimmune Hepatitis were included in the study. There was a decreased association between Autoimmune Hepatitis and Cardiovascular Disease (aOR 0.77, 95% CI 0.69–0.85, p < 0.00), Coronary Artery Disease, (aOR 0.75, 95% CI 0.67–0.85, p < 0.00), and Peripheral Vascular Disease (aOR 0.75, 95% CI 0.60–0.93, p = 0.01). Moreover, Coronary Artery Disease comprises 84% of the overall Cardiovascular Disease cohort and did not demonstrate significantly increased length of stay (aOR ?0.53, 95% CI ?1.16 to 0.12, p = 0.11) or hospitalization cost (aOR ?6711, 95% CI ?14336 to 912, p = 0.08).DiscussionThe decreased association between Autoimmune Hepatitis and Cardiovascular Disease is likely multifactorial in etiology. Consequently, this observation requires further examination with prospective trials.     

Prevalence of Silent Celiac Disease in Patients with Dyspepsia

Celiac disease (CD) has become more common than in the past, although it frequently remains undetected for long periods of time. One reason for this is failure by health care professionals to recognize the variable clinical manifestations of CD and to perform the appropriate tests to make the diagnosis. Although dyspepsia may be part of a clinical spectrum in CD patients, there are scarce data about its prevalence in silent CD. We aimed to determine the prevalence of CD in otherwise healthy dyspeptic patients by means of serologic screening followed by endoscopic biopsies if appropriate. Anti-endomysium antibody assay was positive in 3 of 196 patients. All 3 were female, ages ranged from 19–52 years (mean ± SD age, 36±16 years). Duodenal biopsies were compatible with CD in all, whereas abnormal endoscopic findings were noted in 2. Therefore, a 1.5% prevalence of CD was observed in this study group. The odds ratio for CD was 2.57 (95% confidence interval) in comparison with the general population. CD should be kept in mind as a cause of dyspepsia during clinical activities. The association between these 2 conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for dyspeptic symptoms in CD. During endoscopic examination for dyspepsia, if indicated, endoscopists should carefully inspect the duodenum for CD findings. Although routine serologic screening can not be recommended, it may be appropriate for the patients with refractory dyspepsia, especially females.