Figure 4- - uploaded by Bogdanici Camelia
Content may be subject to copyright.
Source publication
Autoimmune thyroiditis (AT) is a disease that may be associated with many other autoimmune endocrine and non-endocrine disorders. This disease is mediated by both humoral and cellular mechanisms and it is the result of combined effects of human leukocyte antigen (HLA) class II genes and non-HLA genes polymorphisms. The clinical course of AT is vari...
Citations
... Autoimmune thyroiditis refers to an organ-specific autoimmune disease characterised by structural destruction of thyroid tissue and hypothyroidism caused by lymphocyte-infiltrating autoantibodies (TPOAb and TgAb) in the thyroid tissue. 1 High titers of TgAb are present in most patients with AIT (40%-70%), and more than 80% of patients with AIT have high titers of TPOAb. 2 In general, the diagnosis can be confirmed by thyroid ultrasound and antibody testing in clinical practice. The prevalence of AIT is increasing year by year and is much higher in women than in men. 3 The pathogenesis of AIT is unclear and may be related to genetic susceptibility, environmental factors, and endogenous factors. ...
Background
Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear.
Methods
The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively.
Results
Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group.
Conclusion
Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.
... Hashimoto thyroiditis is characterized by clinical hypothyroidism and the presence of auto-antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb) (2). TPO is the key enzyme that oxidizes iodide to iodine that will be incorporated into thyroglobulin for the synthesis of thyroxine (T4) or triiodothyronine (T3) (5). TPOAb, the predominant antibody in autoimmune hypothyroidism, has been reported to be present in over 90% of patients and serves as a useful biomarker to identify disease without a need for thyroid biopsy or surgery (1). ...
Autoimmune thyroid diseases are multifaceted conditions in which the thyroid gland is infiltrated by lymphocytes, resulting in the production of thyroid-specific auto-antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb). Iron deficiency is a common nutritional deficiency and has multiple adverse effects on thyroid metabolism. The association between iron status and thyroid autoimmunity has not been well-evaluated. This retrospective study aimed to determine whether the frequency of iron deficiency was higher in patients with thyroid autoimmunity than in healthy individuals with negative thyroid autoantibodies. One-hundred-and-eighty female patients with positive thyroid auto-antibodies and 81 healthy controls were involved in the study. Hemoglobin, hematocrit, mean corpuscular volume (MCV), iron, thyrotropin (TSH), TPOAb, TGAb, free-T4, vitamin B12, ferritin and transferrin saturation (TS) were recorded. TSH, TPOAb and TGAb levels were significantly higher, while hemoglobin, hematocrit, MCV, ferritin, iron and TS were significantly lower in the patient group (all, p<0.05). Patients with thyroid autoimmunity had significantly higher frequency of lower levels of hemoglobin, iron, ferritin, MCV and TS than healthy controls (all, p<0.005). Correlations were found inversely between TPOAb and serum ferritin, iron, and TS levels, and also positively between TGAb and creatinine levels in the patient group. In conclusion, we found increased prevalence of iron deficiency in female patients with thyroid autoimmunity. Patients with autoimmune thyroid diseases were found to be at higher risk of iron deficiency development.
... From a morphological point of view, HT contains a rich lymphocytic infiltrate predominantly disposed in follicles with germinal center formation. In this case, lymphocytes are predominantly T-cells subtype [19]. ...
Objective:
Identifying the morphological features of thymus in patients with myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) antibodies and concomitant Hashimoto's thyroiditis (HT), which were recruited from a single surgical unit of a tertiary referral hospital located in the North-Eastern region of Romania, over a period of 11 years.
Patients, materials and methods:
We retrospectively reviewed clinical, imaging, laboratory, thymic pathology, and outcome data that were obtained from medical records of patients with MG and concomitant HT, to whom a thymectomy was performed for a suspected thymic lesion. All the surgical interventions were done in the Third Clinic of Surgery, St. Spiridon Emergency County Hospital, Iaşi, Romania, for an 11 years' period, i.e., from January 1, 2000 and December 31, 2010.
Results:
Four patients (three females and one male) were included. The mean age of the patients at the time of their thymectomy was 40.25 years. Of all patients, 75% had moderate or severe MG, 100% had anti-AChR antibodies, and an electromyographic decrement greater than 25%. All patients have been diagnosed with HT in their past medical history by a full thyroid panel [high thyroid-stimulating hormone (TSH) values, low free thyroxine (fT4) values, and the presence of the anti-thyroid antibodies] and all of them have been treated with Euthyrox. Our four patients expressed different MG subtypes, each of them being associated with different thymus pathology. Thoracic computed tomography (CT) scan revealed heterogeneous mediastinal masses and established the correct diagnosis only in 25% of cases. The pathological exams also revealed a heterogeneous pattern of thymic lesions. In contrast with other studies, our patients with MG with anti-AChR antibodies and concomitant HT presented atrophic thymus more frequently (50%), but with particular morphological changes of Hassall's corpuscles. Also, 25% of cases were diagnosed with thymic lympho-follicular hyperplasia (TLFH) associated with thymic epithelial hyperplasia. In B2 thymoma, neoplastic epithelial cells expressed cytokeratin 19 (CK19) immunoreactivity, high Ki67 labeling index and strong p63 immunopositivity.
Conclusions:
In our series, MG and HT occurred simultaneously, or one of them was diagnosed before the other, raising some new questions regarding the immune mechanism of these two autoimmune diseases. Due to the heterogeneous morphological changes of the thymus that we found in this study, we can hypothesize that thymus is involved in the pathogenic mechanism of MG with anti-AChR-antibodies and concomitant HT development.
... Autoimmune thyroiditis (AIT), the most common expressions of which are Hashimoto's disease and Graves' disease (GD), is an organ-speci c autoimmune disease characterized by the destruction of thyroid structure and hypofunction, which is caused by lymphocyte in ltration following the invasion of autoantibodies, mainly thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) into the thyroid tissue [1] . High titers of TgAb exist in most patients with AIT (40%-70%), and TPOAbs are present in most patients with AIT (>80%) [2] . ...
Transcriptomics was used to analyze the protective effect of diosgenin on autoimmune thyroiditis (AIT) in rats and its possible mechanism. Forty AIT model rats were established following high iodine induction and injection of porcine thyroglobulin adjuvant into Lewis rats. AIT-model rats were treated with an oral gavage(diosgenin) for 8 weeks. The concentrations of T3, T4, FT3, FT4, TSH, TRAb, TPOAb and TgAb in rat serum were detected. The unilateral thyroid lobes of rats were detected by transcriptomes, RT-qPCR (S100A9, PKA, Creb, Epac, and Rap1 mRNA), and Immunohistochemistry (cAMP, PKA, and Creb). The results showed that the expression of serum T3, T4, FT3, FT4, TSH, TgAb, and TPOAb in the high-dose group was greater than that in the low and middle-dose groups. And compared with the AIT-model group, the relative expression of cAMP, PKA and Creb mRNA and protein increased, S100A9 mRNA decreased in the diosgenin groups. To sum up, diosgenin can improve the expression of T3, T4, FT3, FT4, and TSH in AIT model rats, and decrease the concentrations of TRAb, TgAb and TPOAb, which may be related to activation of the cAMP/PKA/Creb pathway and downregulating the expression of S100A9 gene.
... Lymphocytes produce antibodies to thyroid peroxidase, thyroglobulin, and thyroid-stimulating hormone receptor and other proteins. AIT is characterized by wide invasion of the thyroid with lymphocytes and macrophages, which generates autoreactivity associated with Tand B-cells [3][4][5]. ...
The peripheral blood mononuclear cells (PBMC) mainly includes monocytes and lymphocytes involved in the development of diabetes mellitus and other autoimmune diseases. Ret/Ras/Raf/MEK/ERK is a signaling cascade that controls cellular processes such as proliferation, survival, angiogenesis, cell growth and motility. The aim of the
work was to study the activation of the main effector protein kinase of this cascade — ЕRК1/2 in PBMC of patients with diabetes and autoimmune (Hashimoto’s) thyroiditis. Material and methods. The material of this work was the blood of healthy subjects, patients with type 2 diabetes, with type 2 diabetes and AIT, with type 2 diabetes and cancer (papillary thyroid carcinoma), with type 1 diabetes, with type 1 diabetes and AIT. Enzyme-linked immunosorbent assay kit 85-86012 («Invitrogen», USA) were used to determine the amount of phospho-ЕRК1/2 (p-Thr202/Thr204, Thr185/Tyr187, respectively). Results. Patients were divided into 6 groups: 1 — control — healthy subjects, representative for age and BMI, 2 — patients with type 2 diabetes, 3 — patients with type 2 diabetes and AIT, 4 — patients with type 2 diabetes and thyroid cancer, 5 — patients with type 1 diabetes, 6 — patients with type 1 diabetes and AIT. It was shown that activation of ЕRК1/2 in PBMC of patients with type 2 diabetes and cancer was not observed, while
in patients with type 1 diabetes or autoimmune thyroiditis it increased significantly. However, in patients with type 1 diabetes with autoimmune thyroiditis, the activation of ЕRК1/2 in PBMC decreased to a control level, which can be explained by the competition between the two autoimmune processes for common signaling pathways. Conclusion.
In PBMC of patients with autoimmune diseases (type 1 diabetes or AIT), MAPK/ERK cascade is activated.
Keywords: peripheral blood mononuclear cells, extracellular signal-regulated kinase-1/2, type 1 and type 2 diabetes, cancer, autoimmune thyroiditis.
... антитіла до пероксидази ЩЗ, тиреоглобуліну, рецептора тиреотропного гормону та інших білків. При АІТ спостерігається широка інвазія ЩЗ лімфоцитами і макрофагами, яка породжує аутореактивність, пов'язану з Т-і В-клітинами [3,4]. ...
... антитіла до пероксидази ЩЗ, тиреоглобуліну, рецептора тиреотропного гормону та інших білків. При АІТ спостерігається широка інвазія ЩЗ лімфоцитами і макрофагами, яка породжує аутореактивність, пов'язану з Т-і В-клітинами [3,4]. ...
MAPK ACTIVATION IN HUMAN BLOOD MONONUCLEAR CELLS IN TYPE 1 AND 2 DIABETES
The peripheral blood mononuclear cells (PBMC) mainly includes monocytes and lymphocytes involved in the development of diabetes mellitus and other autoimmune diseases. Ret/Ras/Raf/MEK/ERK (mitogen-activated protein kinases, MAPK) is a signaling cascade that controls cellular processes such as proliferation, survival,
angiogenesis, cell growth, and motility. The aim of the work was to study the activation in PBMC of the main effector protein kinase of this cascade — ЕRК1/2. Enzyme-linked immunosorbent assay kits were used to determine the amount of phospho-ЕRК1/2.
It is shown that activation of ЕRК1/2 in PBMC of patients with type 2 diabetes is not observed, while in patients with it increased significantly type 1 diabetes or autoimmune thyroiditis. However, in patients with type 1 diabetes with autoimmune thyroiditis, the activation of ЕRК1/2 in PBMC decreases to a control level, which can be explained by the competition between the two autoimmune processes for common signaling pathways.
The role of the MAPK cascade in the pathogenesis of autoimmune diseases is discussed.
Keywords: peripheral blood mononuclear cells, mitogen-activated protein kinases, types 1 and 2 diabetes, autoimmune thyroiditis.
... [7] This form of autoimmune thyroiditis has also been categorized as having a genetic disease, having combined effects of human leukocyte antigen (HLA) class II genes and non-HLA gene polymorphisms contributing to the pathogenesis of the same. [8] The peak age incidence of HT in our study was the third to fourth decade of life, which is in accordance with other Indian studies unlike the Western literature (fifth decade of life). [2,9,10] Female predominance was seen in our study with a female: male ratio of 14.7:1, similar to other studies. ...
Introduction:
Hashimoto's thyroiditis (HT) is a well-known autoimmune disorder of the thyroid diagnosed on fine needle aspiration cytology (FNAC) and a common cause of hypothyroidism in women. Often serological and hematological parameters are additional investigations aiding the diagnosis of this entity.
Aim:
To grade HT based on cytomorphology and to correlate the cytological grades with thyroid hormone status and basic hematological parameters.
Materials and methods:
During a period of 2.5 years, 1762 patients underwent FNAC of thyroid at our tertiary healthcare center. Cytological evidence of lymphocytic thyroiditis was seen in 102 cases, of which 58 cases in addition had thyroid hormone levels and hematological parameters for correlation.
Results:
Of the 58 cases, 55 were females. Majority of the patients had grade II thyroiditis (56.9%), followed by grade I (34.5%) and grade III (8.6%). Elevated thyroid-stimulating hormone was seen in 74.2% of cases, with 39.7% of patients presenting with subclinical hypothyroidism and 18.9% being euthyroid. Mean hemoglobin was low in all grades, more so in hypothyroid state, while other hematological parameters were normal when correlated with grade and hormonal status without any significant P value.
Conclusion:
Cytomorphological grading of HT can explain the pathogenesis of this autoimmune disease. Subclinical hypothyroidism was significantly observed. There was no significant statistical correlation of cytological grades with thyroid status. In this study, most of the hypothyroid cases had low hemoglobin levels while other basic hematological parameters did not show any statistically significant correlation with the thyroid hormonal status.
... Orbital invasion of BCC is an uncommon event that can lead to increase of ocular morbidity and death. It has also been noted that autoimmune conditions may skin cancer development [26,27]. ...
Basal cell carcinoma (BCC) is the most common type of cancer located in the periocular area. We will present the clinical case of a 63-year-old male patient who was admitted to the 2nd Clinic of Neurosurgery, “Prof. Dr. Nicolae Oblu” Emergency Clinical Hospital, Iaşi, Romania, for an ulcerated tumor of about 0.8×0.7 cm in diameter with rolled edges and central necrosis in the upper eyelid with orbital invasion. According to the patient’s personal history, he also underwent Cortisone treatment for dermatomyositis. The magnetic resonance imaging (MRI) scan revealed behind the cutaneous flap, a lesion with 15/38/19 mm anteroposterior (AP)/transverse (T)/craniocaudal (CC) diameters. The surgeons made the excision of the tumor together with the eyelid remnants, and the left orbit exenteration defect. The histopathological exam of the surgical samples revealed an ulcerated epithelial tumor having its origin in the eyelid epidermis and invading all the thickness of the eyelid toward the palpebral conjunctiva, but also the orbital tissue. Immunohistochemical studies showed positive staining for cytokeratin (CK) AE1/AE3, CK5/6, and CK17, but not for CK7. The Ki-67 labeling index was 12%, suggesting a moderate proliferative activity. The final pathological diagnosis was mixed (nodular and morpheic) eyelid BCC infiltrative into the orbital tissue. Although BCC of the upper eyelid is a rare cancer and generally has a low recurrence risk, in the case of a patient undergoing Cortisone treatment for an autoimmune disease, the tumor may grow more rapidly by invading the neighboring tissues including orbit.
... In our study, 69 patients had ulcerated tumors (57 BCCs, 12 SCCs), neglected many years (more than 10 years in 48 patients with BCC, 2-5 years in 21 cases with SCC). It has also been noted that autoimmune conditions may promote the development of skin cancer [21][22][23]. ...
Purpose:
The face is an unfortunate location for any type of tumor - malignant or not - with significant esthetic and functional outcomes. To reconstruct a facial defect may seem simple, but can be rather complicated. The aim of this study is to analyze and discuss our results in order to conclude with specific surgical strategies correlated with the morphopathological results. The most important objective for us is to offer the highest level of expertise to our patients and to prove that the symbiosis between the surgical treatment and the work of the Department of Morphopathology is essential in order to maximize the quality of medical care provided for our patients.
Patients, materials and methods:
A retrospective study was conducted on 116 patients diagnosed with facial malignant tumors, 70 of which were confirmed as basal cell carcinomas (BCCs), 35 confirmed as squamous cell carcinomas (SCCs) and 11 malignant melanomas (MMs). Most BCC cases (57) showed ulceration, with a long clinical evolution (more than 10 years) in 48 cases. Only in 12 SCC cases, patients showed inflammation and ulceration, with a shorter evolution period (2-5 years). For complete microscopic diagnosis, immunohistochemical (IHC) examination was necessary in 46 cases. The BCC "deceiving" clinical behavior and the generally aggressive character of the MM were found in our patients as well.
Results:
The most frequent sites were the orbital region (27 cases) and the nasolabial sulcus (26 cases). In order to reconstruct the postexcisional defects, we had to perform local flaps in 62 cases (14 frontal flaps for orbital defects, 32 glabellar flaps for medial epicanthus, lower lid and nasal region, 15 nasolabial flaps for lower lid or nasal alae and one "Z"-plasty for the submental region). Oncological follow-up was performed in all patients and in 15 cases re-excision was necessary (11 BCCs, two SCCs and two MMs). Cervical lymph node metastasis occurred in six cases (three BCCs, one SCC and two MMs).
Conclusions:
The cooperation between surgeons and pathologists allowed for good outcomes and the pathology examination can guide the surgical approach towards better results both functionally and esthetically.
