The correlation between Epstein Barr-Virus DNA Levels and serum IL-17 in rheumatoid arthritis -

Abstract

Background: The Herpesviridae is a large family of viruses that includes more than a hundred members. Human herpes viruses are large, enveloped, double stranded DNA viruses known for establishing latency and recurrent reactivations. The Epstein-Barr virus (EBV), a herpes virus, infects mostly the B lymphocytes and epithelial cells and establishes latency within memory B cells. The virus then recurrently reactivates and replicates. EBV infection has been previously associated with rheumatoid arthritis (RA), a chronically progressive autoimmune disease. RA is characterized by chronic synovitis and damage of cartilage and bone. IL-17, a proinflammatory cytokine, is produced by Th17 T-lymphocytes as well as other cell types such as monocytes, neutrophils, and natural killer T (NKT) cells. IL-17 is believed to underlie proinflammatory pathways in several autoimmune diseases including RA. In a previous study conducted at the Department of Experimental Pathology, Immunology, and Microbiology, injection of EBV DNA led to enhanced IL-17 production in mice. Therefore, EBV may lead to increased levels of IL-17 in other mammalian systems, such as in humans. Hence, we hypothesize that due to the capability of this virus to cause persistent and repeated infections, its continuous production of DNA would augment autoimmune promoting factors such as IL-17. To assess this possibility we examined whether the EBV DNA load correlates with IL-17 levels in 24 RA patients and 24 non-RA controls. Methods: Upon obtaining subject consent, blood samples were withdrawn. Peripheral blood mononuclear cells (PBMCs) were then separated from blood samples with Ficoll-isopaque. PBMC DNA was then extracted and quantitative PCR (qPCR) was conducted to assess EBV DNA copy numbers. On the other hand, IL-17 levels were measured in sera samples using an enzyme-linked immunosorbent assay (ELISA). Results: The average level of EBV DNA copy number per 106 PBMCs was 31.73 x 103 in control samples whereas it was 31608.23 x 103 in RA samples ind