Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Persistent viral infections can induce aberrant immune responses and are implicated in the development of autoimmunity. Parvovirus B19 (B19V) non-structural protein, NS1, a helicase, covalently modifies self dsDNA and induces apoptosis. This study was undertaken to determine whether resulting apoptotic bodies (ApoBods) containing virally modified dsDNA could induce autoimmunity in an animal model.
Methods: Non-autoimmune BALB/c mice were inoculated with B19V NS1, pristane or staurosporine induced ApoBods and serum tested for dsDNA autoantibodies by Crithidia luciliae staining and ELISA. Brain, heart, liver and kidney pathology was examined by bright field and confocal microscopies. Deposition of self-antigens and ApoBods in glomeruli was examined by staining with labeling antibodies to dsDNA, histones H1 and H4, and TATA-binding protein.
Results: Innoculation with B19V NS1-induced ApoBods induced dsDNA autoantibodies in a dose dependent fashion, whereas staurosporine induced ApoBods did not. Histopathological features of immune mediated organ damage was evident in pristane-induced and B19V NS1-induced ApoBod groups and severity score was significantly higher in these groups than in staurosporine treated groups, and was B19V NS1-induced ApoBod dose dependent. Nucleosomal antigens were deposited in pristane-induced and B19V NS1-induced ApoBod groups, but not in the staurosporine-induced ApoBod group.
Conclusion: This study demonstrated proof of principle in an animal model that virally modified dsDNA in apoptotic bodies could break tolerance to self dsDNA and induce dsDNA autoantibodies and end-organ damage. The study helps explain observations suggesting a viral contribution to the development of systemic lupus erythematosus.
To cite this abstract in AMA style:Naides SJ, Puttaraksa K, Pirttinen H, Gilbert L. Apoptotic Bodies Containing dsDNA Covalently Modified By Parvovirus B19 Non-Structural Protein NS1 Induce dsDNA Autoantibodies and End Organ Damage in Non-Autoimmune Mice [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/apoptotic-bodies-containing-dsdna-covalently-modified-by-parvovirus-b19-non-structural-protein-ns1-induce-dsdna-autoantibodies-and-end-organ-damage-in-non-autoimmune-mice/. Accessed January 19, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/apoptotic-bodies-containing-dsdna-covalently-modified-by-parvovirus-b19-non-structural-protein-ns1-induce-dsdna-autoantibodies-and-end-organ-damage-in-non-autoimmune-mice/