Detection of a Unique Viral Infection in Salivary Glands of Sjögren's Syndrome Patients and Viral-Mediated Recapitulation of Disease in Vivo

Melodie Weller¹, Matthew Gardner¹, Zoe Bogus¹, Michael Smith¹, Elisa Astorri², Drew Michael¹, Changyu Zheng¹, Peter Burbelo³, Paul A. Wilson⁴, Zhennan Lai¹, Bill Swaim¹, Beverly Handelman¹, Sandra Afione¹, Michele Bombardieri² and John A. Chiorini¹, ¹Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, ²Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom, ³Clinical Dental Research Core, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, ⁴National Intramural Database, Division of Enterprise and Custom Applications, Center for Information Technology, National Institutes of Health, Bethesda, MD

Meeting: ACR/ARHP Annual Meeting 2015

Date of first publication: September 29, 2015

Keywords: Hepatitis, infection and viruses, SICCA, Sjogren's syndrome

Session Information

Date: Monday, November 9, 2015

Title: Infection-related Rheumatic Disease: Poster Session

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

A viral infection is thought to be one of the triggers in the development of primary Sjögren’s syndrome (pSS). Multiple studies have shown stimulation of antiviral response pathways in pSS tissues further suggesting the role viral infections may play in disease pathogenesis and/or progression. Yet with this data in hand, a true cause and effect relationship between a viral infection and development of Sjögren’s syndrome had not been identified. Therefore, a study was designed to further define the viral landscape within the affected salivary gland tissue of Sjögren’s syndrome patients and to identify potential viral-mediated triggers of this autoimmune disease.

Methods:

To better understand the viral signatures present in salivary gland tissue, a viral microarray was developed to assess the viral transcripts present in healthy salivary glands compared to patients diagnosed with primary Sjögren’s syndrome. All pSS subjects studied met the American European criteria for pSS. Viral antigens were expressed in salivary glands of female C57BL/6 mice using adeno-associated viral vectors and monitored for changes in stimulated saliva flow, lymphocytic infiltrate formation and development of autoantibodies.

Results:

Two distinct viral profiles were identified by microarray analysis in the Sjögren’s syndrome patients evaluated. One of the profiles identified the presence of hepatitis delta virus (HDV) in 50% of the primary Sjögren’s syndrome cohort. Presence of HDV sequence and antigens were confirmed in two patient cohorts and HDV sequence was confirmed by an independent lab. Patients positive for HDV in salivary gland tissue were negative for detectible hepatitis B virus (HBV) antigen and antibody in serum and presented with normal transaminase levels. In vivo analysis of HDV antigen expression in salivary glands of female C57BL/6 mice resulted in a pSS-like phenotype including reduced saliva flow, increased lymphocytic infiltrates, and development of autoantibodies.

Conclusion:

Identification of HDV in Sjögren’s syndrome patients and induction of a Sjögren’s syndrome-like disease in vivo further support a viral-mediated etiopathology in Sjögren’s syndrome.

Disclosure: M. Weller, None; M. Gardner, None; Z. Bogus, None; M. Smith, None; E. Astorri, None; D. Michael, None; C. Zheng, None; P. Burbelo, None; P. A. Wilson, None; Z. Lai, None; B. Swaim, None; B. Handelman, None; S. Afione, None; M. Bombardieri, None; J. A. Chiorini, None.

To cite this abstract in AMA style:

Weller M, Gardner M, Bogus Z, Smith M, Astorri E, Michael D, Zheng C, Burbelo P, Wilson PA, Lai Z, Swaim B, Handelman B, Afione S, Bombardieri M, Chiorini JA. Detection of a Unique Viral Infection in Salivary Glands of Sjögren’s Syndrome Patients and Viral-Mediated Recapitulation of Disease in Vivo [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/detection-of-a-unique-viral-infection-in-salivary-glands-of-sjogrens-syndrome-patients-and-viral-mediated-recapitulation-of-disease-in-vivo/. Accessed .

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