Fetal microchimeric cells in blood of women with an autoimmune thyroid disease

Context

Hashimoto''s thyroiditis (HT) and Graves'' disease (GD), two autoimmune thyroid diseases (AITD), occur more frequently in women than in men and show an increased incidence in the years following parturition. Persisting fetal cells could play a role in the development of these diseases.

Objective

Aim of this study was to detect and characterize fetal cells in blood of postpartum women with and without an AITD.

Participants

Eleven patients with an AITD and ten healthy volunteers, all given birth to a son maximum 5 years before analysis, and three women who never had been pregnant, were included. None of them had any other disease of the thyroid which could interfere with the results obtained.

Methods

Fluorescence in situ hybridization (FISH) and repeated FISH were used to count the number of male fetal cells. Furthermore, the fetal cells were further characterized.

Results

In patients with HT, 7 to 11 fetal cells per 1.000.000 maternal cells were detected, compared to 14 to 29 fetal cells in patients with GD (p = 0,0061). In patients with HT, mainly fetal CD8⁺ T cells were found, while in patients with GD, fetal B and CD4⁺ T cells were detected. In healthy volunteers with son, 0 to 5 fetal cells were observed, which was significantly less than the number observed in patients (p<0,05). In women who never had been pregnant, no male cells were detected.

Conclusion

This study shows a clear association between fetal microchimeric cells and autoimmune thyroid diseases.     

Analysis of skewed X-chromosome inactivation in females with rheumatoid arthritis and autoimmune thyroid diseases

Introduction  

The majority of autoimmune diseases such as rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) are characterized by a striking female predominance superimposed on a predisposing genetic background. The role of extremely skewed X-chromosome inactivation (XCI) has been questioned in the pathogenesis of several autoimmune diseases.     

Identification of a variant form of tyrosine phosphatase LYP

Background  

Protein tyrosine phosphatases (PTPs) are important cell signaling regulators with major pathological implications. LYP (also known as PTPN22) is an intracellular enzyme initially found to be predominately expressed in lymphocytes. Importantly, an allelic R620W variant of LYP is strongly associated with multiple autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and autoimmune thyroid disease.     

Prevalence of celiac disease in multiple sclerosis

Background  

Celiac disease (CD) is a common systemic disease related to a permanent intolerance to gluten and is often associated with different autoimmune and neurological diseases. Its mean prevalence in the general population is 1-2% worldwide. Our aim was to study the prevalence of celiac disease in a prospective series of Multiple Sclerosis (MS) patients and their first-degree relatives.     

Higher Risk of Thyroid Disorders in Young Patients with Type 1 Diabetes: A 12-Year Nationwide,Population-Based,Retrospective Cohort Study

Background

The association between type 1 diabetes and thyroid autoimmunity has been studied in various populations, but seldom on Taiwanese children and adolescents. Therefore, the aim of this study was to examine the incidence of autoimmune thyroid disorders in Taiwanese children and adolescent patients with type 1 diabetes, based on data from a nationwide, population-based, health claims database.

Methods

Using Taiwan’s National Health Insurance Research Database, we identified 3,652 patients with type 1 diabetes between 2000 and 2012. A comparison cohort was assembled, which consisted of five patients without type 1 diabetes, based on frequency matching for sex and 3-year age interval, for each patient with type 1 diabetes. Both groups were followed until diagnosis of thyroid disorders or the end of the follow-up period. Poisson regression models were used to calculate incidence rate ratios for the thyroid disorders between the type 1 diabetes cohort and the comparison cohort.

Results

Simple and unspecified goiter (International Classification of Diseases, 9^th Revision, Clinical Modification [ICD-9-CM] code 240), thyrotoxicosis (ICD-9-CM code 242), unspecified hypothyroidism (ICD-9-CM code 244.9), and thyroiditis (ICD-9-CM code 245) showed significantly higher incidences in the type 1 diabetes cohort compared with the control cohort, with incidence rate ratios of 2.74, 6.95, 6.54, 16.07, respectively.

Conclusions

Findings from this nationwide, population-based cohort study showed that the incidences of autoimmune thyroid disorders were significantly higher in Taiwanese children and adolescents with type 1 diabetes compared with those without the disease.     

Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity

Introduction  

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. Previous studies have suggested that interferon-lambda 1 (IFN-λ1), a type III interferon, plays an immunomodulatory role. In this study we investigated its role in SLE, including its correlation with disease activity, organ disorder and production of chemokines.     

Early atherosclerosis in systemic sclerosis and its relation to disease or traditional risk factors

Introduction  

Several systemic autoimmune diseases are associated with an increased prevalence of atherosclerosis which could not be explained by traditional risk factors alone. In systemic sclerosis (SSc), microvascular abnormalities are well recognized. Previous studies have suggested an increased prevalence of macrovascular disease as well. We compared patients with SSc to healthy controls for signs of early atherosclerosis by measuring intima-media thickness (IMT) of the common carotid artery in relation to traditional risk factors and markers of endothelial activation.     

Patients with Systemic Lupus Erythematosus Have Higher Prevalence of Thyroid Autoantibodies: A Systematic Review and Meta-Analysis

Background

Thyroid autoimmunity is considered the most common type of organ-specific autoimmune disorder and can be associated with other autoimmune endocrine disorders or non-endocrine diseases. Systemic lupus erythematosus is a prototypical autoimmune disorder with multifactorial etiology. The pathogenesis and development of the disease may result from a loss of immune tolerance and the resulting synthesis of autoantibodies against nuclear antigens. Autoimmune factors may be common features of both thyroid autoimmunity and systemic lupus erythematosus, making it likely that both conditions may coexist within some patients.

Methods and Findings

A number of studies have investigated whether an association between thyroid autoimmunity and systemic lupus erythematosus exists. However, the results of these studies have been inconsistent. Furthermore, most of these studies have had relatively small sample sizes, which have rendered them insufficiently powerful to determine whether there is an association between systemic lupus erythematosus and thyroid autoimmunity. The main objective of this meta-analysis is to provide reliable estimates of the extent of any association between thyroid autoimmunity and systemic lupus erythematosus by combining the primary data from all relevant studies. Literature databases were searched, including the Medline, Embase, Web of Science, Chinese Wanfang and CBM databases, from January 1970 to May 2014. A total of 1076 systemic lupus erythematosus cases and 1661 healthy controls were included in this study. From these data, the odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were calculated. The meta-analysis results showed that the prevalence of thyroid autoantibody positivity in patients with systemic lupus erythematosus was higher than in healthy controls (TgAb: OR = 2.99, 95% CI = 1.83–4.89; TPOAb: OR = 2.20, 95% CI = 1.27–3.82, respectively).

Conclusion

The results of this meta-analysis suggest that thyroid autoimmunity is more prevalent in patients with systemic lupus erythematosus than in a control group.     

Treatment of refractory epilepsy with natalizumab in a patient with multiple sclerosis. Case report

Background  

Multiple sclerosis (MS) is considered an autoimmune disease of the central nervous system and therapeutic inhibition of leukocyte migration with natalizumab, an anti-alpha4 integrin antibody, is highly effective in patients with MS. Recent studies performed in experimental animal models with relevance to human disease suggested a key role for blood-brain barrier damage and leukocyte trafficking mechanisms also in the pathogenesis of epilepsy. In addition, vascular alterations and increased leukocyte accumulation into the brain were recently documented in patients with refractory epilepsy independently on the disease etiology.     

Increase in IL-21 producing T-cells in patients with systemic lupus erythematosus

Introduction  

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by a disturbed T-cell balance skewed towards effector T-cells, in particular Th17-cells. The novel cytokine interleukin-21 (IL-21) is suggested to be crucial for triggering T-cell responses towards IL-17 producing cells. Thus, we aimed to investigate the ability of T-cells to produce IL-21 and IL-17 in SLE patients.     

Underexpression of mitochondrial-DNA encoded ATP synthesis-related genes and DNA repair genes in systemic lupus erythematosus

Introduction  

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by various systemic symptoms and multiple organ damage. We clarify biological and functional abnormalities in SLE by comparing the gene expression profiles of SLE patients with those of healthy individuals.     

Serum 25-Hydroxyvitamin D Deficiency in Chinese Patients with Vitiligo: A Case-Control Study

Background

Low vitamin D levels have been noted in patients with a variety of autoimmune diseases. A recent study showed that low vitamin D levels may be associated with vitiligo.

Objectives

To assess 25-hydroxyvitamin D (25(OH)D) status in Chinese patients with vitiligo in comparison of normal controls and explore possible affecting factors.

Methods

We performed a case-control study including 171 patients, 50 controls in 25(OH)D lowest months and 30 patients, 20 controls in 25(OH)D highest months. Demographic and clinical variables of patients were analyzed to determine the correlation with 25(OH) D levels.

Results

25(OH)D mean value of patients was highest in September and October, lowest in March. None of the patients and normal controls had ‘sufficient’ 25(OH)D (> = 75 nmol/L). No significant difference was found in either 25(OH)D mean values or insufficiency/deficiency ratio between patients and controls in 25(OH)D highest and lowest periods. Female patients were at a higher risk of 25(OH)D deficiency than male patients(P = 0.019). For non-segmental type, patients with 25(OH)D deficiency were more likely to have autoimmune thyroid disease than those with insufficiency (P = 0.016). Sex (P = 0.035), thyroid conditions (p = 0.034), testing month (p = 0.049) were independent factors affecting 25(OH)D level in multivariate analysis.

Conclusion

Chinese population lack 25(OH)D universally. 25(OH)D level shows no correlation with onset of vitiligo in Chinese. However deficient 25(OH)D level may be linked to autoimmune disorders in patients.     

Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis as revealed by DNA microarray analysis

Introduction  

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis that progresses to destruction of cartilage and bone. Bone marrow (BM) cells have been shown to contribute to this pathogenesis. In this study, we compared differentially expressed molecules in BM cells from RA and osteoarthritis (OA) patients and analyzed abnormal regulatory networks to identify the role of BM cells in RA.     

Follistatin-like protein 1 is elevated in systemic autoimmune diseases and correlated with disease activity in patients with rheumatoid arthritis

Introduction

Follistatin-like protein 1 (FSTL1) is a proinflammation mediator implicated in arthritis in rodent animal models. The present study is aimed at assessing FSTL1 levels in systemic autoimmune diseases and correlating them with disease activity in patients with rheumatoid arthritis (RA).

Methods

Serum FSTL1 levels from 487 patients with systemic autoimmune diseases and 69 healthy individuals were measured by enzyme-linked immunosorbent assay (ELISA). FSTL1 expression in synovial fluid (SF) and synovial tissues (STs) was determined by ELISA, immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and western blot analysis in RA patients and trauma controls. FSTL1 levels in fibroblast-like synoviocytes (FLSs) from RA patients were determined by real-time PCR and western blot analysis.

Results

Serum FSTL1 levels were significantly elevated in patients with RA, ulcerative colitis, systemic lupus erythematosus, Sjögren's syndrome (SS), systemic sclerosis and polymyositis/dermatomyositis. Serum FSTL1 levels in the RA and secondary SS patients were substantially higher than those in other patients. Serum FSTL1 levels were increased in early RA, rheumatoid factor (RF)- and anti-cyclic citrullinated peptide antibody (ACPA)-negative patients compared to healthy controls. Moreover, serum FSTL1 concentrations were significantly higher in long-standing RA patients than in early RA patients and in the RF- and ACPA-positive RA patients than in RF- and ACPA-negative RA patients. Elevated FSTL1 levels in the STs and SF of RA patients were also observed. FSTL1 levels in serum were markedly higher than those in SF in RA patients. The strongest FSTL1 staining was detected in the cytoplasm of synovial and capillary endothelial cells from RA synovium. Furthermore, FSTL1 was induced in FLSs by inflammatory mediators. Importantly, serum FSTL1 levels were correlated with several important biologic and clinical markers of disease activity, including erythrocyte sedimentation rate, C-reactive protein, RF, ACPA, swollen joint count, patient global visual analogue scale score and Disease Activity Score 28 in the adult RA patient population. Notably, serum FSTL1 levels were significantly diminished following successful treatment and clinical improvement.

Conclusions

Elevated FSTL1 levels reflect not only joint diseases but also inflammation and tissue degradation in systemic autoimmune diseases. Serum FSTL1 levels may thus serve as a serological inflammatory marker of disease activity in RA patients.     

Dynamic activation of bone morphogenetic protein signaling in collagen-induced arthritis supports their role in joint homeostasis and disease

Introduction  

Rheumatoid arthritis is a chronic systemic autoimmune disease affecting peripheral joints and leading to loss of joint function. The severity and outcome of disease are dependent on the balance between inflammatory/destructive and homeostatic or repair pathways. Increasing evidence suggests a role for bone morphogenetic protein (BMP) signaling in joint homeostasis and disease.     

Plasma cytokine profiles in systemic sclerosis: associations with autoantibody subsets and clinical manifestations

Introduction  

Systemic sclerosis (SSc) (scleroderma) is a complex autoimmune disease that clinically manifests as progressive fibrosis of the skin and internal organs. Anti-centromere antibodies (ACAs), anti-topoisomerase antibodies (ATAs), and anti-RNA polymerase III antibodies (ARAs) are three mutually exclusive SSc-associated autoantibodies that correlate with distinct clinical subsets characterized by extent of cutaneous involvement and pattern of organ involvement. The current report sought to determine whether plasma cytokine profiles differ in SSc patients grouped according to these SSc-associated autoantibody subsets.     

Vitamin D deficiency in rheumatoid arthritis: prevalence,determinants and associations with disease activity and disability

Introduction  

The aim of this study was to estimate the prevalence and determinants of vitamin D deficiency in patients with rheumatoid arthritis (RA) as compared to healthy controls and to analyze the association between 25-hydroxyvitamin D (25(OH)D) with disease activity and disability.     

Thyroid disease is a favorable prognostic factor in achieving sustained virologic response in chronic hepatitis C undergoing combination therapy: A nested case control study

Background

Interferon-α in combination with ribavirin is the current gold standard for treatment of chronic hepatitis C. It is unknown if the development of autoimmune thyroid disease (TD) during treatment confers an improved chance of achieving sustained virologic response. The aim of this study is to assess the chance of achieving sustained virologic response (SVR) in patients who developed TD during treatment when compared with those who did not.

Methods

We performed a tertiary hospital-based retrospective nested case-control analysis of 19 patients treated for hepatitis C who developed thyroid disease, and 76 controls (matched for age, weight, gender, cirrhosis and aminotransferase levels) who did not develop TD during treatment. Multivariate logistic-regression models were used to compare cases and controls.

Results

The development of TD was associated with a high likelihood of achieving SVR (odds ratio, 6.0; 95% confidence interval, 1.5 to 24.6) for the pooled group containing all genotypes. The likelihood of achieving SVR was increased in individuals with genotype 1 HCV infection who developed TD (odds ratio, 5.2; 95% confidence interval, 1.2 to 22.3), and all genotype 3 patients who developed TD achieved SVR.

Conclusions

Development of TD during treatment for hepatitis C infection is associated with a significantly increased chance of achieving SVR. The pathophysiogical mechanisms for this observation remain to be determined.

Trial Registration

The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRB12610000830099     

Behavioural symptoms in patients with Alzheimer's disease and their association with cognitive impairment

Background  

Behavioural and psychological symptoms of dementia (BPSD) are non-cognitive symptoms commonly associated to Alzheimer's disease (AD). The characterization of the clinical profile of AD patients might help to better understand disease evolution and to improve diagnosis and treatment. Thus, the aim of the present study is to describe the clinical profile of AD patients, and to correlate the presence of BPSD with the severity of the disease.     

Decreased serum level of IL-7 in patients with active Graves’ disease

BackgroundGraves’ disease (GD) is a common autoimmune disease which is one of the major causes of hyperthyroidism. Interleukin 7 (IL-7) has been recently reported to play an important role in various autoimmune diseases, but its role in the pathogenesis of GD has not been assessed. The aim of this study was to evaluate the levels of IL-7 and the soluble form of its receptor (sIL-7R) in the serum of GD patients, and to identify their association with disease activity.MethodsA total of 37 GD patients were enrolled into the experimental group and 16 individuals into the control group. All patients were further classified into three subgroups: a GD-active group (hyperthyroidism and TRAb (thyroid stimulating hormone receptor antibody) >7.5 U/L) (N = 15), a GD-inactive group (euthyreosis and TRAb < 1 U/L) (N = 8), and other GD patients (euthyreosis and TRAb > 1 U/L) (N = 14). Concentrations of IL-7 and sIL-7R were assayed with ELISA. Additionally, the relationship between IL-7 and sIL-7R serum concentrations with disease activity (free triiodothyronine [FT3], free thyroxine [FT4], thyroid stimulating hormone [TSH] and TRAb) was also analyzed.ResultsThe serum concentrations of IL-7 in GD-active patients were significantly lower than those of the control group as well as the GD-inactive and GD-other groups. The serum level of IL-7 in GD patients negatively correlated with FT4 and TRAb concentrations. Moreover, no significant difference was observed in the serum level of sIL-7R in GD patients compared to the control group.ConclusionsThese observations suggest that IL-7 may play a role in the pathogenesis of GD and may be associated with its clinical activity. To this end, the serum level of IL-7 could be an additional diagnostic biomarker predictive of the disease and could be particularly valuable for TRAb-negative GD patients.