Intrathyroidal persistence of human parvovirus B19 DNA in a patient with Hashimoto's thyroiditis

doi:10.1016/j.jinf.2007.05.173

Journal of Infection

Volume 55, Issue 2, August 2007, Pages e29-e31

https://doi.org/10.1016/j.jinf.2007.05.173 Get rights and content

Summary

Previous studies suggest a role of viral infection in the development of Hashimoto's thyroiditis (HT). Here we report a patient with HT in whom human parvovirus B19 (B19) DNA has been persistently detected in the thyroid regardless of the presence or absence of B19 DNA in peripheral blood mononuclear cells. In contrast to the DNA persistence, however, VP1 capsid protein was not detected in the thyroid by immunohistochemical studies. Thyroid specimens obtained by fine needle aspiration biopsy from two patients with HT and two with Graves' disease were negative for B19 DNA. Thus, whereas a causal link between B19 infection and HT remains to be determined, B19 DNA may persist in the thyroid and B19 infection may facilitate the intrathyroidal inflammatory process in HT patients.

Introduction

Human parvovirus B19 (B19) infection is associated with a variety of clinical manifestations such as polyarthritis in adults¹ and implicated as a cause or trigger of various autoimmune disorders.² B19 DNA has been detected in peripheral blood mononuclear cells (PBMC), bone marrow cells and synovial samples of patients with chronic B19-associated arthritis.³ In addition, the presence of B19 DNA has been demonstrated in skin, bone marrow and liver tissues of anti-B19 IgG-seropositive subjects,4, 5, 6 suggesting that B19 DNA commonly exists in human tissues. However, its presence has not been reported in the thyroid tissue. Here we report a patient with Hashimoto's thyroiditis (HT) in whom B19 DNA has been persistently detected in the thyroid.

Section snippets

Case report

A 37-year-old Japanese woman suffered from low grade fever, lassitude, lymphadenopathy, skin rash, and arthralgia in June 2000. She had no significant past medical history and her family had been free from autoimmune diseases or thyroid disorders. Serological tests and polymerase chain reaction (PCR) amplifications of VP region of B19³ revealed the presence of serum anti-B19 IgM antibodies and B19 DNA in peripheral blood mononuclear cells (PBMC), respectively (Table 1), leading to a diagnosis

Discussion

HT is a common autoimmune thyroid disease characterized by mononuclear cell infiltration in the thyroid and the presence of serum TgAb and TPOAb, resulting in the destruction of follicles and loss of thyroid function.⁷ Whereas the etiology of HT is not fully understood, some studies suggest an etiological role of viral infection in the development of HT.⁸ To date, only a few studies suggest the association of B19 infection with thyroid diseases.9, 10 However, they did not examine B19 DNA in the

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Parvovirus and Autoimmune Diseases
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For decades, the role of viruses in the initiation and exacerbation of autoimmune disorders have been widely documented. Recently, a growing number of studies have been questioning the relationship between human parvovirus B19 infection and autoimmune disorders. The reason behind a possible association was based on three key findings: (1) the similarities of the clinical manifestations of parvovirus B19 infection with certain autoimmune diseases such as systemic lupus erythematosus (SLE); (2) the production of parvovirus B19 viral protein-induced antibody against self-antigens such as cardiolipin, single-stranded DNA, keratin, and collagen type II; (3) high prevalence of parvovirus B19 DNA as well as positive serological tests of parvovirus B19 in patients with autoimmune diseases. However, the virus-host interactions leading to autoimmune response after parvovirus B19 infection remain uncertain. Nevertheless, three mechanisms were proposed as an explanation for evoking an autoimmune response following infection: molecular mimicry, self-antigen presenting to T cells caused by parvovirus B19-induced erythroblast apoptosis, and the phospholipase activity of the unique region of parvovirus B19 VP1 protein. In fact, the importance of revealing the role of parvovirus B19 infection in autoimmune response particularly in the light of new therapeutic perspectives cannot be overemphasized. Therefore, in this chapter we review the mechanisms related to autoimmune disorders secondary to parvovirus B19 infection. Diseases such as SLE, autoimmune-mediated heart diseases like myocarditis and dilated cardiomyopathy, as well as autoimmune hemolytic anemia are all presented and discussed.
High prevalence of parvovirus B19 infection in patients with thyroid nodules: A case-control study
2022, American Journal of Otolaryngology - Head and Neck Medicine and Surgery
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Therefore, in the present study, we measured the serum level of IgG antibodies against parvovirus B19 to detect infections [18,29,30]. Considering the limited information in the literature on the association of parvovirus B19 infection with autoimmune thyroid disorders [31,32] and the potential association of Hashimoto's and PTC [33], although we did not measure Anti-thyroid peroxidase and Anti-thyroglobulin, only euthyroid patients were included in the study. Previous studies used immunohistochemistry to evaluate parvovirus B19 infection in patients with PTC [11,13,32], benign thyroid nodules [11,32,34], and normal thyroid tissue [11,32].
The incidence of thyroid nodules has increased dramatically in recent decades.
Although this increase has been attributed to improved imaging modalities, the question arises as to whether other environmental factors, such as infectious agents are influential.
Adult patients with newly diagnosed papillary thyroid carcinoma, benign thyroid nodules, and healthy euthyroid controls without nodules; were recruited. Various clinical and biochemical parameters including thyroid function tests and serum Parvovirus B19 Ab (IgG) were assessed and compared between groups.
In this study, data from 364 patients with papillary thyroid carcinoma, 370 patients with benign thyroid nodules, and 360 healthy euthyroid individuals without nodules were analyzed as a control group. The prevalence of parvovirus B19 infection in papillary thyroid carcinoma patients was 58.8% that was significantly higher than the two groups of benign thyroid nodules (49.2%) and the control group (45.0%). In the papillary thyroid carcinoma group, a significant positive correlation was found between tumor size and TSH (r = 0.129, p = 0.014), and between tumor size and B19-Ab (r = 0.176, p = 0.001).
The rate of parvovirus B19 infection was higher in patients with papillary thyroid carcinoma and benign thyroid nodules than in the control group. Also, patients with papillary thyroid carcinoma had significantly higher rates of B19 infection than those with benign thyroid nodules.
Detection of human parvovirus B19 infection in the thymus of patients with thymic hyperplasia-associated myasthenia gravis
2019, Clinical Microbiology and Infection
To investigate the association between myasthenia gravis (MG) and human parvovirus B19 (B19V) infection in the thymus.
The presence of human B19V DNA and protein was assessed in 138 samples—including 68 thymic hyperplasias (39 with MG), 58 thymomas (23 with MG), and 12 normal thymus tissues—using a nested polymerase chain reaction, immunohistochemistry, laser capture microdissection, and sequencing in a double-blinded manner.
B19V DNA was detected mainly in thymic hyperplasia, and the positivity rate (41.18%, 28/68) was significantly higher than that in thymoma (3.45%, 2/58) (p <0.001) but not that in normal thymic tissues. Correspondingly, the positivity rate in thymic hyperplasia with MG (30.77%, 12/39) was significantly higher than that in thymoma with MG (4.35%, 1/23) (p=0.021). However, it was higher in thymic hyperplasia without MG (55.17%, 16/29) than in thymic hyperplasia with MG (30.77%, 12/39) (p=0.043). Cells in thymic hyperplasia positive for B19V VP1/VP2 protein (63.24%, 43/68) were identified mainly in ectopic germinal centres and thymic corpuscle epithelial cells, but were rare in thymomas (1.72%, 1/58) (p <0.001). Moreover, the positivity rate was significantly higher in thymic hyperplasia with MG (74.36%, 29/39) than in thymic hyperplasia without MG (48.28%, 14/29) (p=0.027).
To our knowledge, the present study is the first to show that human B19V infection is closely associated with thymic hyperplasia and thymic-hyperplasia-associated MG, but is not related to thymoma or thymoma-associated MG. The findings reveal a previously unrecognized aetiopathogenic mechanism of thymic-hyperplasia-associated MG, evoking numerous questions that require further investigation.
The microbiota and autoimmunity: Their role in thyroid autoimmune diseases
2017, Clinical Immunology
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Nevertheless, several years earlier, Zhou and colleagues ruled out the induction of pathological inflammation in a mouse model of experimental autoimmune thyroiditis due to a bacterium of the same genus, namely Bifidobacterium lactis [207]. Viruses and their role in AITD have also been discussed and corresponding nucleic acid has been detected via PCR-based methods and immunochemistry [30,31,208], but viruses are beyond the scope of this review. Overall, a large number of studies showed epidemiological, serological and molecular evidence that YE and other bacteria are potentially important in the pathogenesis of AITD and GD.
Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject.
PRDM1 expression via human parvovirus B19 infection plays a role in the pathogenesis of Hashimoto thyroiditis
2015, Human Pathology
Citation Excerpt :
We detected both PVB19 DNA and viral protein in HT, suggesting that PVB19 related to HT in some way. Mori et al [7] reported that both PVB19 DNA and protein are present in an HT case in 2007. Lehmann et al [6] suggested that PVB19 infections are involved in the pathogenesis of some cases of HT in children.
Ectopic lymphoid follicle infiltration is a key event in Hashimoto thyroiditis (HT). Positive regulatory domain zinc finger protein 1 (PRDM1), which is induced by antigen stimulation, can regulate all lymphocyte lineages. Several groups independently demonstrated that human parvovirus B19 (PVB19) is closely associated with HT. Hence, we determined whether PRDM1 is expressed in HT thyroid tissue and whether there is any correlation between PRDM1 expression and PVB19 in the pathogenesis of HT. We detected PRDM1 expression in HT (n = 86), normal thyroid tissue (n = 30), and nontoxic nodular goiter (n = 20) samples using immunohistochemistry. We also detected PVB19 protein in HT samples in a double-blind manner and analyzed the correlation between the 2 proteins using immunofluorescence confocal detection and coimmunoprecipitation. Furthermore, we detected changes of the expression levels of PRDM1 and PVB19 in transfected primary thyroid follicular epithelial cells using real-time quantitative polymerase chain reaction. We found that PRDM1 protein is significantly highly expressed in the injured follicular epithelial cells in HT (83/86 cases) than in normal thyroid cells (0/30 cases) or in nontoxic nodular goiter cells (0/20 cases) (P < .001). In HT, the PRDM1 expression pattern was the same as that of PVB19, whereas PRDM1 and PVB19 were coexistent in the involved epithelial cells. Statistical analysis showed a significant correlation between PRDM1 and PVB19 (P < .001). In addition, primary thyroid epithelial cells also showed PRDM1 up-regulation after PVB19 NS1 transfection. Our findings suggest a previously unrecognized role of PRDM1 and PVB19 in the pathogenesis of HT.
Human parvovirus B19 and autoimmune diseases. Review of the literature and pathophysiological hypotheses
2015, Journal of Clinical Virology
Citation Excerpt :
In contrast, these studies concerning the aetiological role of PVB19 in the pathogenesis of RA were not confirmed by a number of other publications, as some studies have demonstrated persistence of the viral genome in the synovium and synovial fluid in similar proportions of RA patients and controls [65]. More, it is important to keep in mind that the PVB19 DNA might remain persistent, lifelong after primary infection, in almost all types of solid tissues—not only among patients with arthropathy or other inflammatory disorders, but also among constitutionally healthy controls [66–76]. Other serological and molecular biology studies performed on the serum of RA patients and controls failed to demonstrate any significant difference in terms of PVB19 infection.
A number of arguments support the role played by PVB19 in autoimmunity, in the broad sense of the term essentially derived from numerous clinical case reports and/or small series over the past 20–30 years in the medical literature. PVB19 can induce a very broad spectrum of autoantibody production, especially including: anti-soluble nuclear antigen antibodies, antiphospholipid antibodies anti-native DNA antibodies, antilymphocyte antibody, anticardiolipin antibodies, antinuclear antibodies and rheumatoid factor. Notably acute PVB19 infection can mimic or stimulate autoimmune systemic diseases as rheumatoid arthritis or systemic lupus erythematosus. However, at the present time, there is no formal scientific evidence demonstrating a direct role of PVB19 in autoimmunity, bearing in mind that there are also no formal arguments against it. Further large studies are needed to understand the eventual role of PVB19 in autoimmune diseases.

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Case reportIntrathyroidal persistence of human parvovirus B19 DNA in a patient with Hashimoto's thyroiditis

Summary

Introduction

Section snippets

Case report

Discussion

Autoimmunity Rev

Lancet

J Clin Virol

Curr Opin Immunol

Lancet

Blood

Pathogenesis of human parvovirus B19 in rheumatic disease

Ann Rheum Dis

Human parvovirus B19 as a causative agent for rheumatoid arthritis

Proc Natl Acad Sci U S A

Evidence for persistence of parvovirus B19 DNA in livers of adults

J Med Virol

Case report
Intrathyroidal persistence of human parvovirus B19 DNA in a patient with Hashimoto's thyroiditis