Histological, clinical and laboratory findings of acute exacerbation of Hashimoto's thyroiditis--comparison with those of subacute granulomatous thyroiditis

As reported previously, acute exacerbation of Hashimoto's thyroiditis shows quite unique histological findings, namely localized edematous inflammation. Similar histological characteristics and clinical manifestations were observed in 7 of 492 patients with Hashimoto's thyroiditis (A group). Their clinical and laboratory findings were compared with those of 15 cases with subacute granulomatous thyroiditis (S group). Age and sex distribution and goiters in A group were 39 +/- 21 years old (mean +/- s.d.), 7/0 (F/M), and 6/1 (diffuse/nodular), respectively. These were somewhat different from those of S group (45 +/- 9, 12/3, and 3/12, respectively). Thyroid functions in A group showed wide variation: 3 cases were euthyroid, 2 were mildly hypothyroid, and one was mildly thyrotoxic and one borderline thyrotoxic, and all of the S group patients were thyrotoxic. Their thyroid radiopertechnetate uptake, scintigraphy, duration from the onset till the first visit, and ESR and CRP values were also different from those of S group. Clinical courses and outcomes of A group were generally favorable, but one of them finally underwent a total thyroidectomy. Per os and intrathyroidal administrations of steroid were effective, but there was observed a recurrence of symptoms in 3 cases. Finally, all 6 cases were left with diffuse goiters, 4 of them remaining euthyroid, and 2 falling into hypothyroidism. The acute exacerbation of Hashimoto's thyroiditis is a rare complication, which is found to be different from subacute thyroiditis on histological, clinical and laboratory findings and is generally subtle. Steroid medication is considered to be the therapeutic choice but careful observation is necessary to avoid a recurrence.     

Histocompatibility antigens (HLA) in children with lipoid nephrosis]

Actual knowledge on the HLA relationship with the primary glomerulopathies, with particular reference to steroid - sensitive nephrosis of childhood, is surveyed. Occurrence of HLA B-8 and B-35 in this nephropathy has been investigated. The studies involved 47 patients aged between 3 and 15 years and 117 healthy children from Lower Silesian region. It has been showed, that HLA B-8 is present more frequently in sick children, than in healthy controls. The situation is reverse in case of HLA B-35 antigen. However, the difference is statistically insignificant. A probability of the lipid nephrosis sensitivity to corticosteroids can not be predicted on the base of the presence of these HLA antigens.     

Anti-thyroglobulin anti-idiotypic antibodies in sera of patients with Hashimoto's thyroiditis and Graves' disease

The objective of this study was to find naturally occurring anti-idiotypic (anti-Id) antibodies to anti-human thyroglobulin (anti-hTg) idiotype in sera of patients with autoimmune thyroid disease. Sera from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) and sera from normal subjects were tested for the presence of anti-Id antibodies against mouse anti-hTg monoclonal antibodies (McAb) in indirect ELISA and in indirect solid-phase RIA. Microtitration plates were coated with six McAb, five of them directed against different epitopes on hTg molecule, and then incubated with patients' sera. The bound antibody was detected with either peroxidase or 125I-labeled anti-human IgG. The specific positive reaction was observed in four of 40 patients with HT, in two of 26 patients with GD, in seven of 58 patients with RA, and in none of 20 normal subjects. The detected binding was due to the presence of anti-hTg anti-Id antibodies and not to Tg-anti-Tg circulating immune complexes, as the positive sera did not contain hTg when resolved on SDS-PAGE, nor did they bind to all anti-hTg McAb tested. The binding was dose dependent, and titers of anti-Id antibodies varied from 1:243 to 1:2187. The binding could be inhibited up to 50% by hTg, but not by the thyroid microsomal antigen, indicating that some of those anti-Id might represent the internal image of the antigen. Serum from the patient 3403, showing the strongest reactivity against McAb A-3, was chosen for IgG purification and F(ab')2 fragment isolation. The 3403 F(ab')2 fragment, but not the Fc fragment, was found to react specifically with four mouse anti-hTg McAb but not with the control mouse IgG. Thus, the obtained results permit the conclusion that anti-hTg anti-Id antibodies could occur naturally during the course of thyroid autoimmune disorders.     

Histocompatibility antigen changes associated with pink-eyed dilute (p) mutations

The tight linkage between the H-4 histocompatibility locus and the pink-eyed dilute (p) locus raises the possibility that a single gene is responsible for both a histocompatibility antigen and coat color phenotype. To examine this possibility, we have investigated the effects of a spontaneous coat color mutation, pink-eyed unstable (p ^un ), which occurred at the p locus in the C57BL/6J inbred strain, on histocompatibility antigen phenotype. Skin grafts were transplanted from two independently maintained B6 p ^un substrains to coisogenic, wild-type C57BL/6 recipients; graft rejection uniformly commenced at 6–7 weeks but did not culminate in complete graft destruction as observed in other cases of crisis rejection. Neither the onset of rejection time nor the intensity of rejection could be accelerated by introducing new H-2 haplotypes into the wild-type recipients. These results suggested that the p ^un allele was associated with a histocompatibility antigen not shared with C57BL/6. The p ^un allele is characterized by a relatively high frequency of reversion to wild-type. Therefore, skin grafts from B6-p ^un donors were transplanted to homozygous, revertant (+/+) recipients which were subline-matched with the donors; these grafts underwent crisis rejection with the same time of onset of rejection as observed with C57BL/6 recipients. These observations indicate that a new histocompatibility antigen is associated with the p ^un mutation and is lost upon reversion to wild type; this association is the first demonstration of a link between histocompatibility and coat color phenotypes.     

Pathological characteristics of acute exacerbation of Hashimoto's thyroiditis--serial changes in a patient with repeated episodes

A 76-year-old female patient with known Hashimoto's thyroiditis had 12 episodes of acute exacerbation, characterized by high fever and spontaneous pain in the thyroid over a period of 4 months. Percutaneous needle biopsies were performed before and serially after local steroid injection. Histological examination of the thyroid tissue involved obtained before steroid administration revealed quite a unique localized edematous and inflammatory appearance with rich but loosely arranged collagen fibers, and destruction of follicular structures and swollen degenerated epithelia. Neither remarkable cellular infiltrations nor granulomatous changes were observed in the area involved. Ultrasonogram showed an extremely hypoechoic lesion coincident with the location of pain and tenderness. Intrathyroidal administration of triamcinolone acetate (40 mg) resulted in an immediate relief of pain, fever and localized swelling. Surprisingly, remarkable histological improvements were observed even on the day following the injection. However, clinical manifestations as well as histological changes were reversed again within one week or so. After various therapeutic means, total thyroidectomy was performed which induced disappearance of the manifestations. The etiology remains unclear, but pathological findings observed in this patient may provide an insight into the pathogenesis of this rare but intractable condition.     

Expression of hepatocyte growth factor in Hashimoto's thyroiditis with nodular lesions

Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease frequently associated with hyperplastic nodules (HN)s. Hepatocyte growth factor (HGF) is expressed in benign thyroid nodules and over-expressed in malignant thyroid nodules, particularly in papillary thyroid carcinomas. To elucidate the role of HGF in the development of HNs in association with HT we evaluated, by immunohistochemistry, the expression of HGF in both nodular and extranodular tissues, obtained from 30 HTs and 15 goiter samples. Six normal thyroid glands were used as controls. All normal control tissue samples exhibited no evidence of HGF immunoreaction. HNs showed weak to moderate HGF immunoreaction, which was located exclusively in the cytoplasm of stromal cells (fibroblasts and endothelial cells). However, the percentage of positive cases was higher in HNs arisen in the context of HT, compared to HNs not associated with HT (30/30 or 100% vs 4/15 or 40%; p<0.001). HGF immunoreactivity was also detected in all extranodular tissues from HT specimens (30/30 or 100%), but we found some significant differences. In fact, while in HNs observed in the context of HT lesions HGF was expressed only in stromal cells, in the extranodular tissues from the same thyroid gland affected by HT it was also detected in the cytoplasm of the epithelial follicular cells. Furthermore, HTs showed a much higher HGF staining grade in the extranodular tissue compared to HNs. Finally, a clear positive correlation was observed in HT between the proportion of HGF expressing follicular cells and the grade of lymphoid aggregates of the thyroid gland. In conclusion, HGF is much more frequently and highly expressed in thyroid tissue with HT, compared to goiter. In HT glands HGF can be detected in both follicular thyroid cells and stromal cells, while in HNs, either from goiters or associated with HT, its expression is restricted only to the stromal cells. These data indicate that HGF may play a role in cell proliferation processes occurring in thyroid glands affected by HT, probably under the regulation of the lymphoid infiltrate.     

Histocompatibility antigen(s) linked to Rfp-Y (Mhc-like) genes in the chicken

 Major histocompatibility complex (Mhc) genes influencing transplantation rejections were first described in mice within the H2 complex and secondly in chickens within the B complex. In chickens, Rfp-Y haplotypes have recently been identified which contain class I and class II Mhc-like genes that assort independently of the B complex. Three Rfp-Y haplotypes have been defined in a closed breeding flock of line N chickens. In this study, progeny were obtained from line N Rfp-Y heterozygous matings to establish the role of Rfp-Y in transplantation immunity. Rfp-Y incompatibility did not induce significant one-way mixed lymphocyte responses. However, Rfp-Y-incompatible skin grafts were rejected more frequently and at a faster rate than Rfp-Y-compatible grafts by two-week-old chicks. The control Mhc B-incompatible grafts were rejected faster than the Rfp-Y-incompatible grafts; the latter were rejected at speeds that resemble rejection of minor histocompatibility antigens. We conclude that Rfp-Y class I and II Mhc-like genes are linked to the expression of minor histocompatibility antigens in chickens. Received: 21 June 1996 / Revised: 23 July 1996     

Lymphocytes apoptosis in patients with acute exacerbation of asthma

Asthma is characterized by airway inflammation, which can be now assessed by the analysis of induced sputum. Ten patients with asthma were investigated during acute exacerbation for the quantification of apoptosis, for Bcl-2 and Fas expression, in induced sputum lymphocytes. They were compared to 12 patients with chronic obstructive pulmonary disease (COPD), and 10 healthy controls. Spontaneous apoptosis was determined by staining nuclei with propidium iodide, and analyzed with a FACScan. Bcl-2 was measured by Western blotting, and results were obtained by densitometric scanning, done by the gel proanalyser. The investigation of Fas was performed using the streptavidin-biotin preroxidase-complex method. Patients with asthma and patients with COPD exhibited a significant increase of cellularity, percentage of neutrophils, eosinophils and lymphocytes when compared to healthy controls. Apoptosis in induced sputum mononuclear cells was found decreased in patients with asthma compared to COPD patients and healthy controls. The quantification of apoptosis was measured after exposure to anti-cytokine antibodies. Anti-TNF-alpha antibody blocked the apoptosis in both patients groups and healthy controls, suggesting that TNF-alpha acted as an inducer of apoptosis. Anti-IL-10 blocked apoptosis completely exclusively in patients with asthma. Bcl-2 expression was found to be increased in induced sputum mononuclear cells from patients with asthma, compared to healthy controls and patients with COPD. Expression of Fas could be detected in patients with asthma, at a lower level than COPD patients and healthy controls. Distinct mechanisms of apoptosis were found in patients with asthma and patients with COPD, characterized by different levels of Bcl-2 and Fas expression. Induction of apoptosis should be a beneficial process in allergic inflammation traduced in induced sputum mononuclear cells. The apoptosis process is assumed by two different mechanisms in asthma and COPD. Our findings indicated that in asthmatic patients, activated lymphocytes accumulate in the bronchi; because of their prolonged survival that maintains inflammation.     

IgG4乔本甲状腺炎中TRAIL、FasL的表达及临床病理意义

目的探究IgG4乔本甲状腺炎(IgG4Hashimoto's thyroiditis,IgG4HT)的临床、病理、血清学特征,分析血清TRAIL和/或FasL浓度与IgG4HT的临床、病理特征的相关性。方法采用免疫组化检测46例HT组织中的IgG~+、IgG4~+浆细胞,化学发光法及酶联免疫吸附测定法分别检测患者术前血清TgAb,TPOAb和TRAIL、FasL的浓度,并进行分析。结果依据IgG4+浆细胞20/HPF、IgG4~+/IgG~+浆细胞30%的诊断标准,HT组中11例(23.9%)为IgG4 HT。IgG4 HT较非IgG4HT具有更显著的甲状腺纤维化(P=0.006),更易发生亚临床甲状腺功能减退(P=0.02),血清TPOAb水平较低(P0.001),FasL浓度较高(P0.001);血清FasL浓度与IgG4HT甲状腺纤维化程度呈正相关(r=0.620,P=0.042),与甲状腺功能状态呈负相关(r=-0.841,P=0.001)。结论 IgG4HT为更具破坏性的乔本甲状腺炎亚型,FasL可能在甲状腺功能减退进程中发挥作用。     

Aspiration cytology of Hashimoto's thyroiditis in an endemic area

Fine needle aspiration (FNA) plays a significant role in the diagnosis of thyroid lesions due to its simplicity and low cost. Hashimoto's thyroiditis (HT) is the second most common thyroid lesion next to endemic goitre diagnosed on FNA in iodine (I2) deficient areas. Data on its incidence, prevalence and clinicopathological features in I2 deficient areas is scanty compared to I2 sufficient areas. In the present study the patients presented with HT a decade earlier than reported in I2 sufficient areas. Presentation as a nodular thyroid is common. Diagnosis of HT is likely to be missed in smears showing cytological evidence of hyperplasia or abundant colloid. HT was concurrent in 20 cases of endemic goitre. Careful screening for Hurthle cell change and lymphocytic infiltration into follicular cells should be carried out. In equivocal cases multiple punctures and immunological investigations are helpful. In antibody-negative cases repeat FNA at follow-up is useful. Marked lymphocytic infiltration and Hurthle cell change may indicate a hypothyroid state but hormonal levels are required for clinical management.     

甲状腺素钠和地塞米松结合用于桥本甲状腺炎的临床研究

目的观察甲状腺素钠和地塞米松结合用于桥本甲状腺炎的临床效果。方法选取桥本甲状腺炎患者78例,采用简单随机分组法分为实验组和对照组,对照组给予甲状腺素钠治疗,实验组给予甲状腺素钠和地塞米松联合治疗,比较两组患者的临床效果。结果两组患者治疗后的血清游离三碘甲腺原氨酸(FT3)水平无明显变化,与治疗前比较差异无统计学意义(P0.05)。两组治疗后的超敏促甲状腺激素(sTSH)水平低于治疗前,血清游离甲状腺素(FT4)水平高于治疗前,差异均有统计学意义(P0.05)。两组治疗后sTSH、FT4水平比较,差异有统计学意义(P0.05)。结论甲状腺素钠联合地塞米松治疗桥本甲状腺炎的效果显著,值得临床推广应用。     

HLA-DR antigen expression on intrathyroidal lymphocytes and thyrocytes in Hashimoto's thyroiditis and Graves' disease: an immunohistological study

In frozen sections of thyroid glands with Hashimoto's thyroiditis (HT) and Graves' disease (GD), infiltrating lymphocytes were tested for their expression of HLA-DR antigens as a marker of in situ activation. In a combination of indirect immunoperoxidase and direct immunofluorescence staining, most of the immunoglobulin D positive mature B cells were found to be DR positive (DR+) in both diseases. In HT, sizable portions of both helper/inducer T (Leu3+) and suppressor/cytotoxic T (Leu2+) cells were DR+ in interfollicular regions as well as in lymphocyte clusters and lymphoid follicles. In GD, the proportion of DR+ cells in the interfollicular Leu2+ population was significantly lower than that of HT. DR+ thyrocytes were seen in all 14 cases of HT and in 14 out of 16 cases of GD, especially in the vicinity of lymphocyte aggregates. The extent of their DR expression was not correlated with the percentage of DR+ cells in either T subset. These results indicate that a significant portion of infiltrating T cells are activated in autoimmune thyroid diseases, and there may be bidirectional interaction between DR+ thyrocytes and DR+ T cells. The difference in frequency of Leu2+ DR+ cells may account for the difference between the immunopathological features of HT and GD.     

The importance of HLA DQB1*0602 typing in Slovene patients with narcolepsy

The HLA class II region genes DQB1*0602 and DQA1*0102 are currently the best genetic predictors for narcolepsy in humans (1(. The aim of this study was to identify the HLA DQ alleles (DQB1*0602 and DQA1*0102) in Slovene sporadic narcoleptic patients. 11 patients who fulfilled ICSD criteria for narcolepsy entered the study. DRB1*1501 DQB1*0602 was present in all the patients while DQA1*0102 was absent in 2 patients. We propose that DQB1*0602 typing is important in diagnosing narcolepsy in Slovene patients     

Altered N-glycan profile of IgG-depleted serum proteins in Hashimoto's thyroiditis

BackgroundHashimoto's thyroiditis (HT) is an autoimmune disease characterized by chronic inflammation of thyroid gland. Although HT is the most common cause of hypothyroidism, the pathogenesis of this disease is not fully understood. Glycosylation of serum proteins was examined in HT only to a limited extent. The study was designed to determine the glycosylation pattern of IgG-depleted sera from HT patients.MethodsSerum N-glycans released by N-glycosidase F (PNGase F) digestion were analyzed by normal-phase high-performance liquid chromatography (NP-HPLC). N-glycan structures in each collected HPLC fraction were determined by liquid chromatography-mass spectrometry (LC-MS) and exoglycosidase digestion. Fucosylation and sialylation was also analyzed by lectin blotting.ResultsThe results showed an increase of monosialylated tri-antennary structure (A3G3S1) and disialylated diantennary N-glycan with antennary fucose (FA2G2S2). Subsequently, we analyzed the serum N-glycan profile by lectin blotting using lectins specific for fucose and sialic acid. We found a significant decrease of Lens culinaris agglutinin (LCA) staining in HT samples, which resulted from the reduction of α1,6-linked core fucose in HT serum. We also observed an increase of Maackia amurensis II lectin (MAL-II) reaction in HT due to the elevated level of α2,3-sialylation in HT sera.ConclusionsThe detected alterations of serum protein sialylation might be caused by chronic inflammation in HT. The obtained results complete our previous IgG N-glycosylation analysis in autoimmune thyroid patients and show that the altered N-glycosylation of serum proteins is characteristic for autoimmunity process in HT.General SignificanceThyroid autoimmunity is accompanied by changes of serum protein sialylation.