scholarly journals Thyrocytes as the Target Cells for Hhv-6 Infection in Patients with Autoimmune Thyroiditis / Tireocīti Kā Cilvēka Herpesvīrusa-6 Infekcijas Mēríšūnas Pacientiem Ar Autoimūno Tireoidītu

2016 ◽  
Vol 70 (4) ◽  
pp. 160-164
Author(s):  
Alina Sultanova ◽  
Maksims Èistjakovs ◽  
Egils Cunskis ◽  
Katerina Todorova ◽  
Russy Russev ◽  
...  
Keyword(s):  
Viral Load ◽  
Thyroid Gland ◽  
Autoimmune Thyroiditis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Herpesvirus ◽  
Target Cells ◽  
Tissue Samples ◽  
Gland Tissue ◽  
Thyroid Gland Tissue

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.

scholarly journals Presence of B19V in Patients with Thyroid Gland Disorders

Medicina ◽  
2019 ◽  
Vol 55 (12) ◽  
pp. 774
Author(s):  
Sabine Gravelsina ◽  
Zaiga Nora-Krukle ◽  
Simons Svirskis ◽  
Egils Cunskis ◽  
Modra Murovska
Keyword(s):  
Viral Load ◽  
Thyroid Gland ◽  
Viral Infections ◽  
Thyroid Tissue ◽  
Control Group ◽  
Igg Antibodies ◽  
Tissue Samples ◽  
Autoimmune Thyroid ◽  
Gland Tissue ◽  
Thyroid Gland Tissue

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.

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 ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Autoimmune Thyroiditis ◽  
Genomic Sequence ◽  
Thyroid Tissue ◽  
Human Herpesvirus ◽  
Control Group ◽  
Nested Polymerase Chain Reaction ◽  
Tissue Samples ◽  
Reverse Transcription Pcr ◽  
Visual Confirmation

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.

scholarly journals Possible Involvement of Human Herpesvirus-6 U83 Gene Expression in Autoimmune Thyroiditis Development

2019 ◽  
Vol 73 (2) ◽  
pp. 78-83
Author(s):  
Alina Sultanova ◽  
Maksims Čistjakovs ◽  
Lība Sokolovska ◽  
Egils Cunskis ◽  
Modra Murovska
Keyword(s):  
Gene Expression ◽  
Thyroid Gland ◽  
Autoimmune Thyroiditis ◽  
Blood Donors ◽  
Human Herpesvirus ◽  
Control Group ◽  
Human Herpesvirus 6 ◽  
Tissue Samples ◽  
Cytokine Levels ◽  
Herpesvirus 6

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.

Typeability of AmpFlSTR SGM Plus Loci in Brain and Thyroid Gland Tissue Samples Incubated in Different Environments

2007 ◽  
Vol 52 (4) ◽  
pp. 867-869 ◽  
Author(s):  
Anna Niemcunowicz-Janica ◽  
Witold Pepinski ◽  
Jacek R. Janica ◽  
Malgorzata Skawronska ◽  
Jerzy Janica J ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Tissue Samples ◽  
Gland Tissue ◽  
Thyroid Gland Tissue

γ-Interferon Production in Peripheral Blood Mononuclear Cells and Tumor Infiltrating Lymphocytes From Kaposi's Sarcoma Patients: Correlation With the Presence of Human Herpesvirus-8 in Peripheral Blood Mononuclear Cells and Lesional Macrophages

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 968-976 ◽  
Author(s):  
Maria Caterina Sirianni ◽  
Laura Vincenzi ◽  
Valeria Fiorelli ◽  
Simone Topino ◽  
Enrico Scala ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Herpesvirus ◽  
Tumor Infiltrating Lymphocytes ◽  
Skin Lesions ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Infiltrating Lymphocytes

Abstract Evidence indicates that, at least in the early stage, Kaposi's sarcoma (KS) is a cytokine-mediated disease and that it is consistently associated with a novel herpesvirus termed human herpesvirus-8 (HHV-8). To gain insights into the mechanisms by which cytokines and HHV-8 may cooperate in disease pathogenesis, we examined the phenotype, the Th1 (γ-interferon [γIFN]) and Th2 (interleukin-4 [IL-4]) cytokine profile and the presence of HHV-8 in peripheral blood mononuclear cells (PBMC), tumor-infiltrating lymphocytes (TIL), and spindle cell cultures derived from skin lesions of patients affected by classical KS (C-KS) and acquired immunodeficiency syndrome (AIDS)-associated KS (AIDS-KS). TIL and spindle cell cultures were examined at day 0 or after culture in conditioned media from activated T cells (TCM) that contain the same cytokines increased in KS tissues. No differences were found in the immunophenotype of PBMC from C-KS patients versus controls, except for AIDS-KS patients who showed a T-CD8+ expansion. However, a preferential infiltration of T-CD8+ cells was found in all KS lesions examined, which was maintained after culture of TIL in TCM. γIFN production was found in both PBMC and cultures derived from all KS examined; some IL-4 positive supernatants were found only in three AIDS-KS cases. Uninvolved skin did not show appreciable lymphocyte infiltration or cytokine production. The culture conditions of the lesional skin allowed also the appearance of adherent, spindle-like cells bearing markers of tissue macrophages. Finally, most or all of the PBMC, lesions, and macrophagic cell cultures from the skin lesions were found to be positive for HHV-8 infection by nested polymerase chain reaction (PCR). These findings indicate that patients with KS express a Th1 phenotype with a prevalent γIFN production, likely accounted for by the local T-CD8+ infiltration. By analogy with other viral infections (ie, Epstein-Barr virus), this suggests that in loco recruitment of lymphoid cells and the subsequent γIFN production may be in response to or elicited by HHV-8 that was found in both PBMC and macrophagic cell cultures from the lesions of the same patients.

scholarly journals Virome Sequencing in Patients With Myocarditis

2020 ◽  
Vol 13 (7) ◽  
Author(s):  
Bettina Heidecker ◽  
Simon H. Williams ◽  
Komal Jain ◽  
Alexandra Oleynik ◽  
Dimitri Patriki ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Cardiac Tissue ◽  
Mononuclear Cells ◽  
Endogenous Retrovirus ◽  
Fulminant Myocarditis ◽  
Human Endogenous Retrovirus ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Cardiac Tissues ◽  
Barr Virus

Background: Polymerase chain reaction analyses of cardiac tissues have detected viral sequences in up to 67% of cases of myocarditis. However, viruses have not been implicated in giant cell myocarditis (GCM). Furthermore, efforts to detect viruses implicated in myocarditis have been unsuccessful in more accessible samples such as peripheral blood. Methods: We used Virome Capture Sequencing for Vertbrate Viruses (VirCapSeq-VERT), a method that simultaneously screens for all known vertebrate viruses, to investigate viruses in 33 patients with myocarditis. We investigated peripheral blood mononuclear cells (n=24), plasma (n=27), endomyocardial biopsies (n=2), and cardiac tissue samples from explanted hearts (n=13). Results: Nine patients (27%) had GCM and 4 patients (13%) had fulminant myocarditis. We found the following viruses in the blood of patients with myocarditis: Epstein Barr virus (n=11, 41%), human pegivirus (n=1, 4%), human endogenous retrovirus K (n=27, 100%), and anellovirus (n=15, 56%). All tissue samples from fulminant myocarditis (n=2) and GCM (n=13) contained human endogenous retrovirus K. Conclusions: No nucleic acids from viruses previously implicated in myocarditis or other human illnesses were detected in relevant amounts in cardiac tissue samples from GCM or in blood samples from other types of myocarditis. These findings do not exclude a role for viral infection in GCM but do suggest that if viruses are implicated, the mechanism is likely to be indirect rather than due to cytotoxic infection of myocardium.

NK-Cell Reconstitution after HLA-Identical Blood and Marrow Transplantations for CML: The Recovery of NKG2D Is Inversely Correlated with NKG2A and It Promotes the GVL Effect.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4879-4879
Author(s):  
Juan Tong ◽  
Huilan Liu ◽  
Liangquan Geng ◽  
Zimin Sun ◽  
Baolin Tang ◽  
...  
Keyword(s):  
Nk Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Linear Regression Analysis ◽  
Cell Activity ◽  
Target Cells ◽  
Peripheral Blood Stem Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Stem Cells

Abstract Natural killer (NK) cell alloreactivity is reported to mediate strong graft versus leukemia (GVL) effect in patients after allogeneic stem-cell transplantation. NKG2D receptors recognize human MHC class Ichain related A and B (MICA/B) and UL16-binding protein 1∼4(ULBP 1∼4) on target cells, thereby regulating NK cell activity. To examine the recovery of NKG2D, NKG2A and other receptors expression by NK cells, we used flow cytometry to evaluate samples from 11 chronic myeloid leukemia patients and their donors in the year following unmanipulated HLA completely matched peripheral blood stem cells plus bone marrow transplantation. Peripheral blood mononuclear cells from patients and their donors were tested in standard 51Cr release assays against cultured K562 targets to determine the cytotoxicity of the NK cells in the same intervals. There is no mismatched immunoglobulin-like receptor (KIR) ligand in both GVH and HVG direction. The reconstitution of KIR2DL1 (CD158a) after this transplantation protocol was very slow and these receptors didn’t reach normal value in the year and KIR2DL2 (CD158b) was much better. The NKG2D increased and the NKG2A decreased quickly at the same time after engraftment, and used linear regression analysis we demonstrated that NKG2A recovery was inversely correlated with NKG2D recovery in the year following transplantation. The ratio of NKG2D/NKG2A was directly associated with the capacity of NK-cell cytotoxicity. Thus, the reconstitution of NKG2D makes contribution to the recovery of the NK cytotoxicity. These results reveals that the NK cells generated after HLA matched blood plus bone morrow transplantation of CML patients are promoted at an immature state characterized by specific phenotypic features and enhanced functioning, having potential impact for immune responsiveness and transplantation outcome.

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