Abstract
Background:Low-level, chronic viral infections have been suspect in the development of select autoimmune diseases, including primary Sjögren's syndrome (pSS). Multiple studies have shown stimulation of antiviral response pathways in pSS tissues suggestive of a viral infection. Yet, with this data in hand, a causal link between a viral infection and development of pSS had not been identified. Therefore, a study was designed to further define the viral landscape within pSS-affected salivary gland tissue to identify potential viral-mediated triggers in the pathogenesis of this autoimmune disease.Methods:A viral microarray was utilized to measure viral transcripts present in salivary gland tissue from patients diagnosed with pSS compared to healthy controls. Murine models of salivary gland localized HDV antigen expression were developed to evaluate the capacity of a chronic HDV signature to trigger the development of a pSS-like phenotype.Results:Through this analysis, two distinct viral profiles were identified, including the increased presence of hepatitis delta virus (HDV) in 50% of pSS patients evaluated. Presence of HDV antigen and sequence were confirmed in minor salivary gland tissue. Patients with elevated HDV levels in salivary gland tissue were negative for detectible hepatitis B virus (HBV) surface antigen and antibodies to HBV or HDV. Expression of HDV antigens in vivo resulted in reduced stimulated saliva flow, increase in focal lymphocytic infiltrates, and development of autoantibodies.Conclusion:Identification of HDV in pSS patients and induction of a complete pSS-like phenotype in vivo provides further support of a viral-mediated etiopathology in the development of pSS.
Highlights
Viral infections are thought to play a role in the development of chronic diseases, including autoimmune diseases [1]
An additional confirmation study, consisting of 8 primary Sjögren’s syndrome (pSS) and 8 sicca samples, including samples overlapping with those tested in the second phase of the study conducted at the NIH, were analyzed for independent confirmation of hepatitis delta virus (HDV) in RNA isolated from minor salivary gland biopsies conducted at the United Kingdom (UK) location
The viral microarray contained over 3000 probes for viral families known to infect animals
Summary
Viral infections are thought to play a role in the development of chronic diseases, including autoimmune diseases [1]. While evidence of an antiviral response has been observed in multiple autoimmune diseases [2,3,4,5,6,7,8], association with a viral agent has not always been clear This may be attributed to a multifactorial etiology of chronic autoimmunity requiring a genetic susceptibility component in combination with a persistent viral infection or chronic viral exposure to trigger disease pathogenesis. Primary Sjögren’s syndrome (pSS) is an autoimmune disease estimated to affect over 35 million people worldwide [9, 10] This autoimmune disease is currently diagnosed by a reduction in tear and/or saliva secretion, accumulation of focal lymphocytic infiltrates in salivary gland tissue, and development of antibodies against Ro(SSA), La(SSB), and nuclear proteins [11]. A study was designed to further define the viral landscape within pSS-affected salivary gland tissue to identify potential viral-mediated triggers in the pathogenesis of this autoimmune disease
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