Case Report

Rheumatoid arthritis, type 1 diabetes, and Graves' disease after acute parvovirus B19 infection

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.

Rheumatoid arthritis (RA) and autoimmune thyroid disease (AITD) can occur in the same patient in the autoimmune polyglandular syndrome 2. The association of the two conditions has been recognized long-time ago and the prevalence of AITD in patients with RA and vice versa is well assessed. Geographical variation of AITD and related autoantibodies in RA patients is partly due to ethnic and environmental differences of the studied populations. The impacts of thyroid disorders on RA outcome and vice versa are still controversy. In both AITD and RA genetic susceptibility and environmental factors play a synergic role in the development of the diseases. In this review we aimed at investigating the association of AITD and thyroid autoantibodies with RA, the common pathogenic pathways, the correlation with RA disease activity, and influence of the treatment.

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.

Parvovirus B19 is a common human pathogen, which has been linked to autoimmune diseases recently. The aim of the study is to evaluate whether B19 is involved in adult Hashimoto's thyroiditis (HT).

Eighty-six thyroid tissues from the adult patients with a spectrum of thyroid disorders were examined for B19 DNA and capsid protein by nested PCR, in-situ hybridization and immunohistochemistry. The presence of viral DNA in HT epithelium was studied by laser-capture microdissection and sequencing of PCR products. The expressions of nuclear factor-κB (NF-κB) and interleukin-6 were investigated by immunohistochemistry.

B19 DNA was significantly present in HT tissues by both PCR (29/32, 90.6%) and in-situ hybridization (23/32, 71.9%, all p < 0.01) compared with normal thyroid tissue (7/16, 43.8%; 2/16, 12.5%). Laser-capture microdissection further confirmed this difference. B19 capsid protein in HT group was significantly higher than that in all the control groups (p < 0.01), and the expression of NF-κB and interleukin-6 in HT tissues was up-regulated. NF-κB was well co-localized with B19 protein in thyroid epithelia by double-labeling immunofluorescence and confocal microscopy.

The presence of B19 nuclear acid and viral protein was significantly common in HT tissues and it suggested a possible role of B19 in adult HT.