scholarly journals HHV-6 Infection and Chemokine RANTES Signaling Pathway Disturbance in Patients with Autoimmune Thyroiditis

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 689 ◽  
Author(s):  
Alina Sultanova ◽  
Maksims Cistjakovs ◽  
Liba Sokolovska ◽  
Katerina Todorova ◽  
Egils Cunskis ◽  
...  

The aim of this study was to investigate the role of human herpesvirus-6 (HHV-6) in autoimmune thyroiditis (AIT) development. We examined the possible involvement of HHV-6 gene expression encoding immunomodulating proteins U12 and U51 in AIT development and their role in the modulation of chemokine signaling. One hundred patients with autoimmune thyroiditis following thyroidectomy were enrolled in this study. Nested polymerase chain reaction (nPCR) was used to detect the HHV-6 sequence in DNA samples. Reverse transcription PCR (RT-PCR) with three different HHV-6 gene targets (U79/80, U51 and U12) was to detect active infection markers. HHV-6 load was identified using a commercial real-time PCR kit. Immunohistochemistry was performed to investigate the expression of the HHV-6 antigen and RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in thyroid gland tissue. Different commercial immunosorbent assay kits were used for the detection of RANTES, IFNγ, IL-6, and TNFα levels in the AIT patient group and controls. We detected 98% presence of the HHV-6 genomic sequence in AIT patients’ thyroid gland tissues. Markers of active HHV-6 infection (HHV-6 U79/80, U12 and/or U51 mRNA) were predominant in AIT patients’ thyroid tissue samples in comparison with the control group (56% vs. 6%). Evidence from immunofluorescence microscopy showed that HHV-6 can persist in thyrocytes and can interact with RANTES. Visual confirmation of the intense immunofluorescence signal of RANTES detected in thyroid tissues could indicate high expression of this chemokine in the thyroid gland. On the other hand, immunosorbent assays showed very low RANTES levels in AIT patients’ peripheral plasma. These results indicate that RANTES level in AIT patients could be influenced by HHV-6 activation, which in turn may aid AIT development.

Author(s):  
Lība Sokolovska ◽  
Alina Sultanova ◽  
Maksims Čistjakovs ◽  
Egils Cunskis ◽  
Modra Murovska

Abstract The aim of this study was to investigate the possibility of using monocytes/macrophages as mediators in human herpesvirus-6 (HHV-6) infection of thyroid gland tissues in autoimmune thyroiditis (AIT). Seventy-three AIT patients were enrolled in this study. The control group consisted of 80 blood donors. Monocyte/macrophage isolation for AIT patient samples was performed by adherence. HHV-6 was detected in peripheral blood mononuclear cell (PBMC) DNA samples using nested polymerase chain reaction (nPCR). Gene expression of HHV-6 active infection marker (U79/80) and chemokine receptors (U12, U51) in patient monocyte/macrophage samples and blood donor PBMC samples was detected using reverse-transcription PCR. HHV-6 viral load was detected by using quantitative-PCR technique. The HHV-6 genomic sequence was found significantly more frequently among AIT patient than control group samples. Markers of active infection were found in 8 AIT patient monocyte/macrophage samples (11%) and in none of control group PBMC samples. HHV-6 U51 mRNA expression was detected only in AIT patient samples (2/24 previously positive for HHV-6). Since HHV-6 genomic sequences were found significantly more frequently in AIT patient samples and active infection markers were found in patient monocytes/macrophages, our results suggest that monocytes/macrophages may be used by HHV-6 as mediators for thyroid gland infection.


Author(s):  
Alina Sultanova ◽  
Maksims Čistjakovs ◽  
Lība Sokolovska ◽  
Egils Cunskis ◽  
Modra Murovska

Abstract Viral infections have been frequently cited as important environmental factors implicated in autoimmune thyroiditis (AIT) development, although no specific virus has yet been conclusively associated with the disease. Some evidence implicates human herpesvirus-6 (HHV-6) in this disease. The aim of this study was to investigate the role of the HHV-6 U83 gene expression in autoimmune thyroiditis development. Fifty-one patients with AIT following thyroidectomy and a control group of 30 autopsied subjects without thyroid pathologies for comparing virology results and 30 healthy blood donors for comparing serology results were enrolled in this study. HHV-6 U83 gene expression was determined using nested PCR with complementary DNA as the template acquired from thyroid gland extracted RNA. Plasma samples of AIT patients and blood donors were tested for IL-2, IL-4, IL-10, sTNF-RII and IL-1beta levels by ELISA. Virology results were compared with pro- and anti-inflammatory cytokine levels to determine possible interaction of HHV-6 with host immune response. HHV-6 U83 gene expression was found only in 24% (12/49) of AIT patient thyroid gland tissue samples and in none of the control group individuals, showing possible involvement of this gene in AIT development. However, no interaction between HHV-6 and changes in cytokine levels was found.


Author(s):  
Alina Sultanova ◽  
Maksims Èistjakovs ◽  
Egils Cunskis ◽  
Katerina Todorova ◽  
Russy Russev ◽  
...  

Abstract Human herpesvirus-6 (HHV-6) is a ubiquitous betaherpesvirus with immunomodulating properties that have been suggested to play an important role in the development of several autoimmune disorders. Although the primary targets for HHV-6 replication, both in vitro and in vivo, are CD4+ and CD8+ T lymphocytes, some studies have reported the presence of HHV-6 sequences in different solid organs, including in the thyroid gland, showing possible involvement of this herpesvirus in development of autoimmune thyroid disease. The aim of this study was to determine loads of HHV-6 in thyroid gland tissue in comparison to those in peripheral blood of patients with autoimmune thyroiditis. Seven patients [women mean age 45 (28-65)] with histologically confirmed autoimmune thyroiditis were enrolled in this study. Fluorescence-activated cell sorting was used to distinguish and sort lymphocyte populations from peripheral blood mononuclear cells of patients. HHV-6 load was determined by real-time PCR for peripheral blood and thyroid gland tissue samples. Additionally, all results from molecular analyses were compared with histological results obtained by light microscopy. Viral load was detected only in one (46 viral copies/ 1×106cells) blood sample; others were under the detection limit of the used kit. However, in all HHV-6 positive tissue samples viral load was detected in the range of 132-1620 viral copies/106 cells. Substantial HHV-6 load in lymphocyte subpopulations was detected in two of seven patients. HHV-6 load was detected in NK and CD95+ cells of two patients. The obtained results show that thyroid gland cells (tyrocytes) act as target cells for HHV-6.


Medicina ◽  
2019 ◽  
Vol 55 (12) ◽  
pp. 774
Author(s):  
Sabine Gravelsina ◽  
Zaiga Nora-Krukle ◽  
Simons Svirskis ◽  
Egils Cunskis ◽  
Modra Murovska

Background and Objectives: Viral infections are frequently cited as a major environmental factor implicated in thyroid gland diseases. This work aimed to estimate the presence of B19V infection in patients with thyroid gland disorders. Materials and Methods: Thyroid gland tissue and blood samples of 50 patients with autoimmune thyroid gland diseases (AITDs), 76 patients with non-autoimmune thyroid gland diseases (non-AITDs), and 35 deceased subjects whose histories did not show any autoimmune or thyroid diseases (control group) were enrolled in the study. Virus-specific IgM and IgG were detected using ELISA, and the presence and viral load of B19V in the tissue and blood were detected using PCRs. Results: B19V IgG antibodies were detected in 35/50 AITDs patients and in 51/76 non-AITDs patients, and B19V IgM antibodies were detected in 1/50 patients with AITDs and in none of the 76 patients with non-AITDs. The B19V NS sequence was found in the tissue DNA of 10/50 patients with AITDs, in 30/76 with non-AITDs, and in 1/35 control group individuals. The median B19V load in the tissue of patients with AITDs and non-AITDs was 423.00 copies/µg DNA (IQR: 22.50–756.8) and 43.00 copies/µg DNA (IQR: 11.50–826.5), respectively. The viral load in one of the 35 nPCR B19V-positive thyroid tissue samples from the deceased subjects was 13.82 copies/µg DNA. The viral load in the tissue of patients with AITDs was higher than in whole blood, which possibly indicates B19V persistency in thyrocytes (p = 0.0076). Conclusion: The fact that the genoprevalence of B19V NS was significantly higher in patients with non-AITDs compared to the control group and in the thyroid gland tissue of patients with AITDs, and that the non-AITDs viral load was higher than in tissue derived from the control group individuals, suggest the possibility that B19V infection could be involved in the development of thyroid gland diseases.


Author(s):  
Sabīne Grāvelsiņa ◽  
Elisabetta Caselli ◽  
Zaiga Nora-Krūkle ◽  
Simons Svirskis ◽  
Anda Vilmane ◽  
...  

AbstractThe functions of human natural killer cells are controlled by diverse families of antigen receptors. Prominent among these are the killer cell immunoglobulin-like receptors (KIR), controlled by a family of genes clustered in one of the most variable regions of the human genome — on chromosome 19q13.4. This study aimed to investigate the possible interplay between KIR allotype, B19 infection, and thyroid disorders. Thyroid gland tissue of 30 patients with autoimmune thyroid gland diseases (AITD), 30 patients with non-autoimmune thyroid gland diseases (non-AITD) and 30 deceased subjects whose histories did not show any of autoimmune or thyroid diseases (control group) were enrolled in the study. The presence of B19V, KIR2DL2/DS2, and KIR2DL3 was detected using PCRs (nPCR, PCR). The results showed that 28% of samples of thyroid tissue from patients with AITD and 67% with non-AITD were positive for the presence of B19V, in contrast only 5% control tissue samples harbored B19V DNA. B19V-positive AITD patients had higher frequency of KIR2DL2/DS2 homozygosity and lower frequency of homozygous KIR2DL3 genotype compared to B19V negative cases (33% vs 21% and 17% vs 46%, respectively). Although our data showed that B19V positive patients with AITD had a higher frequency of homozygosity for KIR2DL2/DS2, further studies with larger groups of patients are necessary to confirm the relationship between KIR, B19V and susceptibility to thyroid disease.


2021 ◽  
Vol 93 (4) ◽  
pp. 369-375
Author(s):  
Anna R. Khachatryan ◽  
Goar J. Vardanyan ◽  
Garnik A. Avetisyan ◽  
Aram S. Chomoyan ◽  
Satenik E. Baghdasaryan ◽  
...  

Aim. To determine the features of visualization of papillar thyroid cancer (PTC) in presence of autoimmune thyroiditis (AIT) according to sonoelastography data. Materials and methods. 155 patients were examined (75 PTC, 30 AIT, 20 PTC in presence of AIT and 30 with diffuse parenchymal changes) and 30 patients of the control group. Among patients with PTC 68 (90.7%) were represented by female (mean age 46.713.12 years) and 7 (9.3%) by male (average age 48.14.05 years) patients, PTC in presence of AIT by 19 female (average age 46.916.98 years) and 1 male (22 years) patients. Ultrasound investigation was performed with devices Toshiba Aplio-400 and Toshiba Aplio-500 (Japan) by the standard method and using elastography. A surface transducer with a frequency of 1014 MHz was used. An analysis of the thyroid ultrasound image was performed in correspondence with TI-RADS. For a qualitative assessment of the elastographic picture of thyroid foci, the TsukubaUeno assessment visual standardized system was implemented. Results. According to the TI-RADS scale, most nodular formations are assigned to category 4. With TPC with an unchanged thyroid gland, category 4 was determined in 52 patients (69.3%), and with PR in presence of AIT 15 patients (75%). When determining the qualitative criteria for Tsukuba Ueno, the majority of tumors were assigned to types 3b and 4: cancers in presence of AIT 95% and cancers with no changes to thyroid gland 81.3%. Sonoelastographic criteria for thyroid parenchyma with AIT with a high degree of confidence are significantly higher than in the control group (p0.000). In a comparative analysis of thyroid sonoelastography in PTC with unchanged parenchyma and AIT, changes according to compression elastography are statistically unreliable. In shear wave elastography, sonoelastographic criteria for PTC are significantly higher in patients with AIT (p0.02 when measured in kPa, p0.01 when measured in m/s). Conclusion. Sonoelastography data can be used as additional criteria in the differential diagnosis of focal thyroid formations.


Author(s):  
G. G. Gabulov ◽  
G. I. Jabrailova

The authors studied the effect of selenium on the dynamics of immune system indicators in children with autoimmune thyroiditis. They examined 31 children (average age of 11.16 ± 0.59 years). Group I included 17 children who took selenium (100 μg per day for 6 months) along with the basic treatment. Group II (n=14) took L-thyroxin. The control group included 15 healthy children of the same age. The average level of selenium in children of Group I and II was 69.23 ± 1.52 μg / l at the beginning of the study, in the control group it was 114.8 ± 3.18 μg / l. Before treatment, children in Group I and II had T-cell suppression, the average level of all cytokines (especially TNF-α and IL-6) was significantly higher than in practically healthy children. The study demonstrated that the level of the thyroid tissue antibodies decreased significantly (p=0.001) with an increase in the level of selenium in the blood serum. By the end of the study the content of IgA (p=0.012) and IgG (p=0.044) in Group I, as well as the number of lymphocytes CD3 + (p=0.008), CD4 + (p=0.015), CD16 + / 56 + (p=0.010) significantly increased. The authors observed statistically significant decrease in the levels of TNF-α (p=0.028), IL-6 (p=0.002) and IL-1β (p=0.009) in children who took selenium in addition to the main treatment. Thus, the results of the study suggest that selenium in the complex therapy of autoimmune thyroiditis significantly reduces the titer of antithyroid antibodies and positively affects a number of important indicators of immune homeostasis in children.


1972 ◽  
Vol 69 (2) ◽  
pp. 309-320 ◽  
Author(s):  
B.-A. Lamberg ◽  
J. Mäenpää ◽  
V. Kivikangas ◽  
R. Karlsson ◽  
P. Saarinen

ABSTRACT The total iodine content and the content of iodocompounds in the thyroid gland were studied in 9 patients with autoimmune thyroiditis. The thyroids were labelled in vivo with radioactive iodine before surgical biopsy. Five grams of tissue were homogenized and the iodocompounds were separated both by paper chromatography and on a cellulose column. The distribution profile of both the radioactive and the stable compounds was determined. The thyroid tissue contained on an average 11.0 ± 8.0 (sd) per cent of radioactive and 15.0 ± 9.4 per cent of stable iodothyronines. The MIT/DIT ratio was 1.16 ± 0.26 for the radioactive and 0.92 ± 0.30 for the stable compounds. Clinically evident hypothyroidism occurred only in patients with a very low iodine content and was not correlated with the proportion of iodothyronines found in the thyroid tissue. For instance, in two hypothyroid patients the iodothyronines corresponded to about 20 per cent of the iodocompounds of the tissue. These findings suggest that iodine depletion of the thyroid gland plays an important role in the development of clinical hypothyroidism in autoimmune thyroiditis and that up to a very late stage of the disease the thyroid is evidently capable of producing iodothyronines in fairly normal proportions.


2015 ◽  
Vol 14 (1) ◽  
pp. 81-91
Author(s):  
T. V. Saprina ◽  
T. S. Prokhorenko ◽  
N. V. Ryazantseva ◽  
I. N. Vorozhtsova ◽  
S. Yu. Martynova ◽  
...  

Very little research is devoted to the study of communication systemic immunological changes and local immunological changes in the tissue of the thyroid in autoimmune thyrophaties. The goal of the research was to establish immunologic and morphologic predictors of clinical course and functional outcomes of Graves’s disease (GD).Material and methods. We examined 45 patients with GD (14 men and 31 women) aged 18–55 years (47.0 (35.0–53.0)) years, matching the following criteria: a verified diagnosis GD, accommodation in Tomsk oblast and the Tomsk not less than 10 years, the patient's consent for the study. The control group included 30 people, with an average age of (45.3 ± 5.6) years and was comparable by age and sex with GD patients. The study included: definition of the standard for GD hormonal and serological profile (free T4, free T3, and TSH, antibodies to TPO, antibodies to the TSH receptor), the cultivation of mononuclear leukocytes in complete culture medium within 24 hours with subsequent determination of interleukins concentrations (IL-2, IL-4, TNF-alpha) in culture medium using enzyme-linked immunosorbent assay, determination of the number of blood cells carrying membrane-bound receptors to IL-2, IL-4, TNF-R1 by flow laser cytometry on cytometer BD FACS Canto tmΙΙ (USA) using labeled monoclonal antibody, the standard postoperative histological examination of thyroid gland tissue samples and immunohistochemical detection in samples of thyroid tissue receptors to IL-2, IL-4, TNF-alpha.Results. On the basis of the received results it is possible to allocate 2 clinical-immunologic and morphologic cluster of autoimmune hyperthyroidism syndrome in patients with clinical diagnosis of GD. The first includes the formation of 1 and 2 histological options GD (minimally expressed monocytes infiltration, lack of oncocytic transformation of thyroid epithelium), with some clinical characteristics (persistent and pronounced hyperthyroidism, the large size of goiter, higher titer of receptor TSH-antibody and smaller TPO-antibody, diffuse nature of the lesion), and the second – is represented by 3d histological option with oncocytic restructuring of follicular epithelium, expressed the monocyte/macrophage infiltration with the TNF-RI expression and clinical patterns, including: the older age group of patients, the smaller size of goiter, the emergence of “pseudo nodes” ultrasound, reflecting the presence of lymphoid follicles-infiltrates, more lenient for hyperthyroidism. Probably, that the 2nd cluster is a combination of “classical GD” with autoimmune thyroiditis, however, a set of clinical and laboratory-instrumental signs led to the fact that these patients were in the group of GD patients.Conclusion. This approach (combining study of indicators of systemic and local tissue-specific autoimmune inflammation) is a promising from the point of view of separate parts coverage in the autoimmune thyroids diseases pathogenesis, approximating researchers to develop immune based therapeutic technologies.


2013 ◽  
Vol 62 (6) ◽  
pp. 40-46
Author(s):  
Galina Petrovna Pologoyko ◽  
Maria Igorivna Yarmolinskaya ◽  
Tatyana Mihajlovna Lekareva

The article represents influence of gestagen desogestrel on size and function of thyroid gland in women of reproductive age. Into the study we included 70 women who were prescribed gestagen desogestrel in a daily dose of 75 mg for a period of 12 months. All the patients were devided into two groups. The first group consisted of 20 women with diffuse nontoxic goiter, the second consisted of 30 women with autoimmune thyroiditis. Control group consisted of 20 women without thyroid gland pathology. Prior to therapy with desogestrel and after 12 month of treatment, serum levels of free triiodothyronine, free thyroxine and thyrotropin releasing hormone, thyroperoxidase antibodies were determined and thyroid gland sonigraphy was performed in all the patients. Obtained data show that gestagen desogestrel doesn’t influence the size and function of thyroid gland in healthy women and in patients with diffuse non-toxic goiter. In women with autoimmune thyroiditis implication of desogestrel significantly decreases blood levels of thyroperoxidase autoantibodies.


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