title: Increased Epstein-Barr Virus DNA Load and Antibodies Against EBNA1 and EA in Sardinian Patients with Rheumatoid Arthritis.
abstract: A role for Epstein-Barr Virus (EBV) infection in the etiology of autoimmune diseases, including rheumatoid arthritis (RA), has long been suggested. However, data about EBV burden in RA patients from Sardinian population, a genetic isolate with high prevalence of autoimmune diseases, have not yet been reported. One hundred thirty-five, Sardinian subjects (77 RA patients and 58 demographically matched healthy donors, HDs) were enrolled in a cross-sectional case-control study. EBV-DNA was quantified by quantitative real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Prevalence and titers of anti-Early Antigen IgG (anti-EA-IgG) and anti-Epstein-Barr Nuclear Antigen 1 IgG (anti-EBNA-1 IgG) were determined by immunoenzimatic assay. EBV-DNA positivity was more frequent in RA PBMCs than in HD PBMCs (79.2% vs. 56.9% respectively, p=0.008). Similarly EBV relative load was increased in RA than in HD PBMCs [2.83 (6.5) vs. 0.53 (1) 2(-ΔCt) EBV-DNA, respectively, p=0.02]. Moreover, Sardinian RA patients were found to have increased prevalence of anti-EBNA-1 IgG (90% vs. only 69% of HD, p=0.006) and anti-EA IgG (37% compared with only 10.3% of HD, p=0.002). Subgroup analysis revealed that PBMCs from RA receiving Tocilizumab, an anti-interleukin-6 (IL-6) receptor monoclonal inhibitor, have significantly lower EBV viral loads in comparison to PBMCs from RA under other immunosuppressors (p=0.03). These data suggest an association between EBV infection and RA in the Sardinian population. The potential influence of IL-6 inhibition on EBV viral load in RA patients should be further explored in prospective trials.
authors.affiliation: 1 Dipartimento di Medicina Clinica e Sperimentale, Cattedra e Unità di Reumatologia, Università e AOU di Sassari , Sassari, Italy .
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Erre
authors.affiliation: 2 Dipartimento di Scienze Biomediche, Microbiologia Clinica e Sperimentale, Università degli Studi di Sassari , Sassari, Italy .
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mameli
authors.affiliation: 2 Dipartimento di Scienze Biomediche, Microbiologia Clinica e Sperimentale, Università degli Studi di Sassari , Sassari, Italy .
authors.forename: Davide
authors.initials: D
authors.lastname: Cossu
authors.affiliation: 1 Dipartimento di Medicina Clinica e Sperimentale, Cattedra e Unità di Reumatologia, Università e AOU di Sassari , Sassari, Italy .
authors.forename: Benedetta
authors.initials: B
authors.lastname: Muzzeddu
authors.affiliation: 1 Dipartimento di Medicina Clinica e Sperimentale, Cattedra e Unità di Reumatologia, Università e AOU di Sassari , Sassari, Italy .
authors.forename: Cristina
authors.initials: C
authors.lastname: Piras
authors.affiliation: 2 Dipartimento di Scienze Biomediche, Microbiologia Clinica e Sperimentale, Università degli Studi di Sassari , Sassari, Italy .
authors.forename: Daniela
authors.initials: D
authors.lastname: Paccagnini
authors.affiliation: 1 Dipartimento di Medicina Clinica e Sperimentale, Cattedra e Unità di Reumatologia, Università e AOU di Sassari , Sassari, Italy .
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passiu
authors.affiliation: 2 Dipartimento di Scienze Biomediche, Microbiologia Clinica e Sperimentale, Università degli Studi di Sassari , Sassari, Italy .
authors.forename: Leonardo Antonio
authors.initials: LA
authors.lastname: Sechi
mesh_terms: D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral