HLA class I upregulation and antiviral immune responses in Graves' disease

This is the final version. Available on open access from Oxford University Press via the DOI in this record. Data Availability: Restrictions apply to some or all the availability of data generated or analyzed during this study to preserve patient confidentiality. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided.CONTEXT: The origin of Graves' disease (GD) remains elusive. However, evidence of an association between GD and viral infections is emerging. Human leukocyte antigen (HLA) class I presents viral antigens to circulating immune cells and plays a crucial role in the defense against viral infections. OBJECTIVE: To investigate HLA class I expression, enterovirus presence and the viral immune response proteins signal transducer and activation of transcription 1 (STAT1) and protein kinase R (PKR) in thyroid tissue from GD patients. DESIGN AND PATIENTS: We collected thyroid tissue from core needle biopsies or surgical specimens from 48 GD patients and 24 controls. Standard immunohistochemistry was used to detect HLA class I and enteroviral capsid protein 1 (VP1) on formalin-fixed and paraffin-embedded tissue. STAT1 and PKR were examined by combined immunofluorescence staining. MAIN OUTCOME MEASURES: HLA class I expression score. RESULTS: The HLA class I expression score, which takes both proportion and intensity of immunostaining into account, was significantly higher in GDs (3.1±3.3) than in controls (0.5±0.9) (p<0.001). Significantly more VP1 positive thyroid cells were found GD samples (50.1± 30.5%) than in controls (14.9±10.5%) (p<0.001). STAT1 and HLA class I was found within the same thyroid cells and PKR and VP1 were also colocalized within thyroid cells. CONCLUSION: HLA class I is upregulated in GD and enterovirus protein is prevalent in thyroid tissue. The colocalization of HLA class I with STAT1 and VP1 with PKR indicates an antiviral tissue response. These findings support the concept of a link between viral infections and GD.European Union FP7(FP7/2007-2013)South-Eastern Norway Regional Health Authority (Helse Sør-Øst)University of OsloDiabetes Research Foundatio

Immunological changes and increased expression of myxovirus resistance protein a in thyroid tissue of patients with recent onset and untreated Graves' disease

Background: Few studies have systematically examined the immune cells that infiltrate thyroid tissue at the time of the onset of Graves&#39; disease (GD). The role of viruses in the pathogenesis of autoimmune thyroid diseases is controversial. The present study analyzed inflammatory responses with respect to signs of virus infection. Methods: Thyroid tissue was obtained from 22 patients with newly diagnosed and untreated GD, 24 patients with chronic GD, and 24 controls. Inflammation was assessed by immunostaining for CD4+ and CD8+ T cells, plasma cells (CD138+), and plasmacytoid dendritic cells (PDCs). The production of interferon-inducible myxovirus resistance protein A (MxA) was analyzed as a sign of virus infection. Results: The degree of thyroid inflammation and fibrosis was significantly higher in both patient groups compared with that in controls. The number of CD4+ T cells and plasma cells (activated B cells) was significantly higher in both patient groups. CD8+ cells were only present in patients with chronic disease. MxA expression and the number of PDCs increased only in patients with newly diagnosed GD. There was a strong positive correlation between the number of PDCs and the number of MxA+ leucocytes. Conclusion: The increase in CD8+ T cells during the chronic stage of GD suggests that they may play a role in progression of the autoimmune process from early to chronic thyroiditis. Upregulation of MxA expression during the early stages of the disease, and the positive correlation between the number of PDCs and the number of MxA+ leucocytes, suggests that activated PDCs secrete type I IFNs at the lesion site, possibly in response to viral infection. &nbsp;</p

Elevated neutrophil-to-lymphocyte ratio in the diagnosis of Hashimoto's thyroiditis

Aktas, Gulali/0000-0001-7306-5233WOS: 000426268800011PubMed: 29489971Objective: Hashimoto's thyroiditis (HT) is an autoimmune inflammatory disorder. The purpose of this study was to determine the neutrophil-to-lymphocyte ratio (NLR), a novel marker of inflammation, in patients with HT and to compare these values with those from healthy subjects. Method: A total of 154 participants were included in the study, 90 HT patients and 64 healthy volunteers. Retrospectively, demographic and laboratory data of the subjects were obtained from our institution's database. Patients with active infection, diabetes mellitus, malignancy, other chronic inflammatory diseases, hematologic disorders and patients on aspirin or steroid treatment were excluded from the study. Values for complete blood count (CBC) and serum laboratory parameters of HT patients were the baseline values obtained at the time of HT diagnosis. Control subjects consisted of healthy volunteers who visited our institution for a routine check-up. Results: Age, gender and CBC parameters were not different between the HT group and the control group; however, the NLR of HT group (2.1 [1.3-5.8]) was significantly higher than the control group (1.9 [0.6-3.3]), p=0.04. Conclusion: Increased NLR may be useful as an indicator of the presence of HT, especially in complicated cases. NLR is inexpensive and easy to determine. Larger, prospective studies are required to determine its usefulness in assessing diagnostic potential and treatment outcomes in HT patients

A cross-sectional study of hepatitis C among people living with HIV in Cambodia: Prevalence, risk factors, and potential for targeted screening

The epidemiology of hepatitis C in Cambodia is not well-known. We evaluated the prevalence of hepatitis C virus (HCV) and risk factors in the HIV cohort of Sihanouk Hospital Center of Hope in Phnom Penh to strengthen the evidence for suitable HCV testing strategies among people living with HIV (PLWH) in Cambodia. All consenting adult PLWH without a history of HCV treatment were tested for HCV between November 2014 and May 2016 according to the CDC algorithm (HCV antibody II electro-chemiluminescence immunoassay, followed by COBAS® AmpliPrep/COBAS® TaqMan® HCV PCR and INNO-LIA® HCV Score immunoblot end-testing). Genotyping was performed using the line probe assay Versant HCV genotype 2.0®. The study enrolled a total of 3045 patients (43% males, median age: 42.5 years, 55 years (11.2%). Genotype 1b (45%) and 6 (41%) were predominant. Coinfected patients had a higher aspartate-to-platelet ratio index, lower platelets, a lower HBsAg positivity rate and more frequent diabetes. Based on logistic regression, blood transfusion antecedents (adjusted odds ratio 2.9; 95% CI 1.7-4.9), unsafe medical injections (2.0; 1.3-3.2), and partner (3.4; 1.5-7.6) or household member (2.4; 1.3-3.2) with liver disease were independently associated with HCV in women. However, having a tattoo/scarification (1.9; 1.1-3.4) and household member (3.1; 1.3-7.3) with liver disease were associated with HCV in men. Thus, our study found intermediate endemicity of active hepatitis C in a large Cambodian HIV cohort and provides initial arguments for targeted HCV screening (>50 years, partner/household member with liver disease, diabetes, increased aspartate-to-platelet ratio index) as efficient way forward