HLA Class I Upregulation and Antiviral Immune Responses in Graves Disease

Weider, Therese; Richardson, Sarah J.; Morgan, Noel G.; Paulsen, Torbjørn; Dahl‐Jørgensen, Knut; Hammerstad, Sara Salehi

doi:10.1210/clinem/dgaa958

Cited by 10 publications

(8 citation statements)

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“…In human thyroid, viral infection has also been shown to activate interferon signaling and the expression of interferon-stimulated genes (36,49). Moreover, enhanced expression of HLA class I and of interferon-related STAT1 and PKR genes has been demonstrated in the thyroid tissue collection used in this study (9,10).…”

Section: Discussionmentioning

confidence: 72%

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High Prevalence of Common Human Viruses in Thyroid Tissue

et al. 2022

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IntroductionEvidence points to viral infections as possible triggers of autoimmune thyroid disease (AITD), but little is known about the prevalence of common viruses in the thyroid gland. Using a novel approach based on virus enrichment in multiple cell lines followed by detection of the viral genome and visualization of viral proteins, we investigated the presence of multiple human viruses in thyroid tissue from AITD patients and controls.MethodsThyroid tissue was collected by core needle biopsy or during thyroid surgery from 35 patients with AITD (20 Graves’ disease and 15 Hashimoto’s thyroiditis). Eighteen thyroid tissue specimens from patients undergoing neck surgery for reasons other than thyroid autoimmunity served as controls. Specimens were tested for the presence of ten different viruses. Enteroviruses and human herpesvirus 6 were enriched in cell culture before detection by PCR and immunofluorescence, while the remaining viruses were detected by PCR of biopsied tissue.ResultsForty of 53 cases (75%) carried an infectious virus. Notably, 43% of all cases had a single virus, whereas 32% were coinfected by two or more virus types. An enterovirus was found in 27/53 cases (51%), human herpesvirus 6 in 16/53 cases (30%) and parvovirus B19 in 12/53 cases (22%). Epstein-Barr virus and cytomegalovirus were found in a few cases only. Of five gastroenteric virus groups examined, only one was detected in a single specimen. Virus distribution was not statistically different between AITD cases and controls.ConclusionCommon human viruses are highly prevalent in the thyroid gland. This is the first study in which multiple viral agents have been explored in thyroid. It remains to be established whether the detected viruses represent causal agents, possible cofactors or simple bystanders.

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Section: Discussionmentioning

confidence: 72%

“…Enteroviruses (9)(10)(11), parvovirus B19 (12)(13)(14) and hepatitis C virus (HCV) (15,16) have all been associated with AITD. Among herpesviruses, Epstein-Barr virus (EBV) has been associated with GD (17)(18)(19), while human herpes virus 6 (HHV-6) and cytomegalovirus (CMV) may be associated with both HT and GD (20)(21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

High Prevalence of Common Human Viruses in Thyroid Tissue

et al. 2022

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“…Some studies have also examined the relationship between COVID-19 and HLA in patients with certain diseases, such as cancer. For example, no significant allelic relationship was found in the HLA genotype of lung cancer patients with and without COVID-19 [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiological studies have shown an association between various diseases and certain HLA alleles, including those caused by ribonucleic acids (RNA) viruses, such as SARS, influenza, human immunodeficiency virus (HIV), hepatitis C, rabies, and other [ 23 ]. Compared with HLA class II, HLA class I plays a crucial role in viral infection by presenting viral antigens to CD8 + T cells on the surface of infected cells, followed by recognition and destruction of the cells [ 24 ]. The likely effect of T cells in SARS-CoV-2 infection could be illustrated by the response of 40–60% of T cells in unexposed individuals to viral proteins due to a cross-immune reaction with other coronaviruses in previous colds [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

The role of HLA genotypes in understanding the pathogenesis of severe COVID-19

Arab

Mollazadeh

Ghayourbabaei

et al. 2023

Egypt J Med Hum Genet

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The coronavirus disease 2019 (COVID-19) pandemic has caused human tragedy through the global spread of the viral pathogen SARS-CoV-2. Although the underlying factors for the severity of COVID-19 in different people are still unknown, several gene variants can be used as predictors of disease severity, particularly variations in viral receptor genes such as angiotensin-converting enzyme 2 (ACE2) or major histocompatibility complex (MHC) genes. The reaction of the immune system, as the most important defense strategy in the case of viruses, plays a decisive role. The innate immune system is important both as a primary line of defense and as a trigger of the acquired immune response. The HLA-mediated acquired immune response is linked to the acquired immune system. In various diseases, it has been shown that genetic alterations in components of the immune system can play a crucial role in how the body responds to pathogens, especially viruses. One of the most important host genetic factors is the human leukocyte antigen (HLA) profile, which includes HLA classes I and II and may be symbolic of the diversity of immune response and genetic predisposition in disease progression. COVID-19 will have direct contact with the acquired immune system as an intracellular pathogen after exposure to the proteasome and its components through class I HLA. Therefore, it is assumed that in different genotypes of the HLA-I class, an undesirable supply causes an insufficient activation of the immune system. Insufficient binding of antigen delivered by class I HLA to host lymphocytes results in uncertain identification and insufficient activation of the acquired immune system. The absence of secretion of immune cytokines such as interferons, which play an important role in controlling viral infection in the early stages, is a complication of this event. Understanding the allelic diversity of HLA in people infected with coronavirus compared with uninfected people of one race not only allows identification of people with HLA susceptible to COVID-19 but also provides better insight into the behavior of the virus, which helps to take effective preventive and curative measures earlier.

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“…However, in many cases further studies are needed to confirm whether the expression alone is the predisposing factor and how the regulatory variation affects differential expression in diseases. Elevated HLA expression levels have been associated with inflammatory bowel diseases ( 56 , 76 ), scleroderma patients with interstitial lung disease ( 77 ), ankylosing spondylitis ( 78 ), Graves’ disease ( 79 ), systemic lupus erythematosus ( 80 ), rheumatoid arthritis ( 72 ), and multiple sclerosis ( 81 ). Additionally, in celiac disease and type 1 diabetes, higher expression of DQA1*05 and DQB1*02 alleles was found in patients when compared to healthy controls ( 82 , 83 ).…”

Section: Hla Expression In Human Diseasesmentioning

confidence: 99%

HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation

2022

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Varying HLA allele-specific expression levels are associated with human diseases, such as graft versus host disease (GvHD) in hematopoietic stem cell transplantation (HSCT), cytotoxic T cell response and viral load in HIV infection, and the risk of Crohn’s disease. Only recently, RNA-based next generation sequencing (NGS) methodologies with accompanying bioinformatics tools have emerged to quantify HLA allele-specific expression replacing the quantitative PCR (qPCR) -based methods. These novel NGS approaches enable the systematic analysis of the HLA allele-specific expression changes between individuals and between normal and disease phenotypes. Additionally, analyzing HLA allele-specific expression and allele-specific expression loss provide important information for predicting efficacies of novel immune cell therapies. Here, we review available RNA sequencing-based approaches and computational tools for NGS to quantify HLA allele-specific expression. Moreover, we explore recent studies reporting disease associations with differential HLA expression. Finally, we discuss the role of allele-specific expression in HSCT and how considering the expression quantification in recipient-donor matching could improve the outcome of HSCT.

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HLA Class I Upregulation and Antiviral Immune Responses in Graves Disease

Cited by 10 publications

References 50 publications

High Prevalence of Common Human Viruses in Thyroid Tissue

High Prevalence of Common Human Viruses in Thyroid Tissue

The role of HLA genotypes in understanding the pathogenesis of severe COVID-19

HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation

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