Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides.
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Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease. (+info)
The expression and distribution of S-100 protein and CD 83 in thyroid tissues of autoimmune thyroid diseases.
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To investigate the expression and distribution of S-100 protein and CD 83 in the thyroid tissues of autoimmune thyroid diseases (ATDs), and to study the role of the dendritic cells in the pathogenesis of ATDs, immunohistochemical staining was used on pathological tissues of 20 patients with Hashimoto's thyroiditis (HT) and 20 patients with Graves' disease (GD) to check the expression and distribution of S-100 protein and CD 83. Compared with control group (20 cases of thyroid follicular adenoma, TFA), the higher expressions of S-100 in HT (139.38+/-5.92 vs 59.47+/-11.69) and GD (119.42+/-14.48 vs 59.47+/-11.69) were observed respectively (p<0.001). The increased positive expressions of CD 83 which is known as a marker of mature and activated DCs in HT (22.58+/-13.96 vs 5.19+/-8.08) and GD (29.92 +/-14.43 vs 5.19+/-8.08) were also found respectively (p<0.001). Serum TPO antibody (TPO-Ab, 67.3+/-11.6%) and Tg antibody (Tg-Ab, 59.8+/-10.1%) in HT were higher than those in GD (28.4+/-5.7%, 23.1+/-4.9%) and TFA (6.1+/-3.4%, 7.2 +/-4.6%) (p<0.01). Serum TR-Ab in GD (16.3+/-5.6 U/L) was higher than those in HT (4.8+/- 2.3 U/L) and TFA (2.5+/-1.2 U/L) (p<0.01). Our findings suggest that the high expression of DCs' markers may be related to the pathogenesis of HT and GD. The upregulation of both the number and the matured functions of DCs, may lead to present more antigens and to produce more auto-antibodies (such as Tg-Ab and TPO-Ab in HT, TR-Ab in GD), which may be involved in pathogenesis of the autoimmune thyroid diseases. (+info)
Sex-specific association of PTPN22 1858T with type 1 diabetes but not with Hashimoto's thyroiditis or Addison's disease in the German population.
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BACKGROUND: Endocrine autoimmune disorders share genetic susceptibility loci, causing a disordered T-cell activation and homeostasis (HLA class II genes, CTLA-4). Recent studies showed a genetic variation within the PTPN22 gene to be an additional risk factor. MATERIALS AND METHODS: Patients with type 1 diabetes (n = 220), Hashimoto's thyroiditis (n = 94), Addison's disease (n = 121) and healthy controls (n = 239) were genotyped for the gene polymorphism PTPN22 1858 C/T. RESULTS: Our study confirms a significant association between allelic variation of the PTPN22 1858 C/T polymorphism and type 1 diabetes mellitus (T1D). 1858T was observed more frequently in T1D patients (19.3% vs 11.3%, P = 0.0009; odds ratio for allele T = 1.88, 95% confidence interval [1.3-2.7]). Furthermore, we found a strong association in female patients with T1D (P = 0.0003), whereas there was no significant difference between male patients with type 1 diabetes and male controls. No significant difference was observed between the distribution of PTPN22 C/T in patients with Hashimoto's thyroiditis or Addison's disease and healthy controls. CONCLUSION: The PTPN22 polymorphism 1858 C/T may be involved in the pathogenesis of type 1 diabetes mellitus by a sex-specific mechanism that contributes to susceptibility in females. (+info)
Graves' disease and Hashimoto's thyroiditis in monozygotic twins: case study as well as transcriptomic and immunohistological analysis of thyroid tissues.
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OBJECTIVE: To report on the rare simultaneous occurrence of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in monozygotic twins. DESIGN: We compared the pattern of thyroid tissue-derived cDNAs to gain insight into previous and ongoing immune destruction and reconstruction processes using microarrays. The results were confirmed by immunohistology and real-time PCR. RESULTS: Destruction of thyroid tissue in HT reduced levels of thyrocyte-related cDNAs and cDNAs encoding extracellular matrix components, but increased levels of proteases involved in extracellular matrix degradation compared with GD. Lymphocytic infiltrates forming ectopic follicles replaced the thyroid tissue almost completely in HT. Thus, lymphocyte-related cDNA levels were higher in HT than in GD. The same was true for many chemokines and their receptors, which not only enable migration towards the thyroid but also maintain the lymphocytic infiltrate. HT also showed increased levels of cDNAs encoding molecules related to apoptosis than did GD. Surprisingly, the Th1- and Th2-specific cytokine profiles suggested for HT and GD respectively could not be confirmed. cDNAs encoding factors and receptors involved in angiogenesis were increased in GD compared with HT. CONCLUSIONS: Comparison of gene expression reflects the cellular differences between the two types of autoimmune thyroid disease in twins with identical genetic and similar environmental background. (+info)
Association of antipituitary antibody and type 2 iodothyronine deiodinase antibody in patients with autoimmune thyroid disease.
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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. (+info)
Fetal microchimerism in Hashimoto's thyroiditis: a quantitative approach.
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OBJECTIVE: Fetal microchimerism (MCH) has been implicated in the etiology of autoimmune diseases such as autoimmune thyroiditis. The goal of the study was to reliably estimate the number of fetal engrafted cells and to further investigate factors influencing the development of MCH. METHODS: Quantitative real-time PCR amplification using Y-chromosome specific (DYS14) and autosomal (beta-globin) loci was performed on thyroid gland specimens. Furthermore, we compared the distribution of ABO and rhesus systems in mothers with and without blood MCH in relation to the blood groups of the children. RESULTS: MCH was detected in eight of 21 Hashimoto patients in a frequency range of 15 to 4900 male cells per 100,000 total cells (median 97 cells), but in none of 17 healthy thyroid glands. In a third group, consisting of 18 nodular goiters, only one sample was positive (182 male cells/100,000 total cells). No woman who had not had a prior pregnancy with a male fetus showed MCH. Mothers both with and without MCH showed the same rate of mother/child incompatibilities for the ABO and rhesus systems. CONCLUSIONS: The percentage of microchimeric cells varies to a great extent in Hashimoto's thyroiditis, and this phenomenon can occur in nodular goiter in rare instances, but it appears to be absent from normal thyroid glands. Nevertheless, the biological significance of MCH remains unclear. Moreover, we have concluded that the tested blood group systems (as opposed to their role in graft vs host disease after transplantations) have no effect on fetal MCH. (+info)
Restricted kappa/lambda light chain ratio by flow cytometry in germinal center B cells in Hashimoto thyroiditis.
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To determine the diagnostic significance of the kappa/lambda ratio in germinal center (GC) B cells in Hashimoto thyroiditis (HT), we used 4-color flow cytometry to immunophenotype 27 samples (21 patients) of well-characterized HT B-cell clonality was analyzed further by polymerase chain reaction (PCR) of the immunoglobulin heavy chain (IgH) and bcl-2/IgH fusion genes using DNA extracted from aspirate smears and/or paraffin-embedded tissues. By flow cytometric analysis, the CD10+ GC B cells had a higher mean +/- SD kappa/lambda ratio than the CD10- B cells (5.1 +/- 3.3 vs 2.0 +/- 0.8; P < .0001, Student t test). In 18 samples (67%), CD10+ GC B cells had a kappa/lambda ratio greater than 3.07 (the upper limit of kappa/lambda ratio reported in reactive nodes; range, 3.2-14.4 in the 18 cases). Cases tested by PCR showed no evidence of a clonal proliferation. None of 21 cases developed lymphoma during clinical follow-up of up to 3 years. The kappa/lambda ratio of CD10+ GC B cells in HT can be skewed markedly beyond that reported in reactive lymph nodes. This finding frequently is present in HT. Pathologists should be familiar with this phenomenon to prevent misdiagnosis of follicular lymphoma in patients with HT. (+info)
Chronic autoimmune thyroid disease in children and adolescents in the years 1999-2004 in Lower Silesia, Poland.
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The aim of the study was to analyze data related to chronic autoimmune thyroid disease at diagnosis and at follow-up of children and adolescents in Lower Silesia in the years 1999-2004. Age, gender, incidence of thyroid disease in the family, clinical presentation, hormonal findings, levels of thyroid antibodies, results of ultrasonography, and fine needle aspiration biopsy (FNAB) were recorded. 100 children, 10 boys and 90 girls, were included in the analysis. The mean age at diagnosis was 12.3+/-2.3 years and at last examination 14.9+/-1.9 years. At diagnosis, increased levels of TSH without overt hypothyroidism was observed in 26 children. In 11 children hyperthyroidism was detected whereas 63 children were euthyroid. An increased level of thyroid peroxidase antibodies was observed in 65% of the children. Ultrasonography was characteristic for Hashimoto's thyroiditis in all patients. Fine needle biopsy was performed when there were diagnostic difficulties (35% children). Thus, in all the children the diagnosis of Hashimoto's thyroiditis was ascertained either by high antibody titer or FNAB. Associated diseases were observed in 33% of the children. Thyroid disease in the family was present in 25% of the children. There was a gradual decline in the number of new cases presented from 1999 to 2004. The reason for this decline remains speculative. (+info)