Background Support: FAPESP #2010/10013-4, 2010/10017-0 and 2010/13463-0

Antibody to Epstein-Barr virus (EBV) early antigen diffuse (anti-EA-D) is associated with viral replication. However, their possible associations with clinical/therapeutic features in primary Sjögren’s syndrome (pSS) were not established.

Objectives To evaluate the EBV serological profile in pSS patients, considering the current glucocorticoid and immunosuppressive treatments, organic affections and the disease activity score.

Methods We evaluated 100 pSS patients (American-European Criteria) and 89 age/gender/ethnicity-matched healthy controls. Disease activity was measured by EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). Serum antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG and anti-EA-D IgG) were determined by ELISA.

Results Patients and controls had comparable frequencies and mean levels of anti-VCA IgG (90 vs. 86.5%, p=0.501; 2.6±1.1 vs. 2.5±1.1 AU/mL, p=0.737) and anti-EBNA-1 IgG (92 vs. 94.4%, p=0.576; 141.3 ±69.8 vs. 135.6±67.5 RU/mL, p=0.464), with anti-VCA IgM uniformly negative. Noteworthy, higher frequency and increased mean levels of anti-EA-D occurred in patients than controls (36 vs. 4.5%, p<0.0001; 38.6±57.4 vs. 7.9±26.3 RU/mL, p<0.0001). Frequency of anti-EA-D positive (28.6 vs. 4.5%, p=0.0001) and mean levels of this reactivity (30.2±51.5 vs. 7.9±26.3 RU/mL, p=0.0002) were also higher in pSS patients without any glucocorticoid and/or immunosuppressive therapy (n=49) than in healthy controls (n=89), in spite of comparable age (p=0.628), gender (p=1.000) and ethnicity (p=1.000). Further analysis of pSS patients with (n=36) and without (n=64) anti-EA-D revealed comparable age (47.8±11.0 vs. 47.6±10.8 years, p=0.925), gender (female: 100 vs. 95.3%, p=0.551), ethnical distribution (white: 66.7 vs. 67.2%, p=1.000), disease duration (8.9±5.4 vs. 8.3±5.0 years, p=0.578), current prednisone dose (4.8±6.9 vs. 5.1±10.4 mg/day, p=0.319), current uses of prednisone (52.8 vs. 37.5%, p=0.148) and immunosuppressants (44.4 vs. 31.3%, p=0.201). ESSDAI-values were comparable (p=0.102), but joint activity (ESSDAI criteria) was more frequent (25 vs. 9.4%, p=0.045) in anti-EA-D positive patients. Anti-EA-D was not associated with anti-Ro-SSA (p=1.000), anti-La-SSB (p=0.652), rheumatoid factor (p=1.000), anti-alpha-fodrin (p=0.390) or antiphospholipid antibodies (p=0.573), not suggesting cross-reactivity.

Conclusions The finding of elevated serum levels of anti-EA-D antibody even in the absence of glucocorticoid or immunosuppressive treatment suggests the involvement of EBV in the pathogenesis of pSS. In addition, the new association of anti-EA-D with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.

Disclosure of Interest S. Pasoto Grant/Research support from: Agency for Promotion of Research (FAPESP), R. Natalino Grant/Research support from: Agency for Promotion of Research (FAPESP), H. Chakkour Grant/Research support from: Agency for Promotion of Research (FAPESP), V. Viana: None Declared, C. Bueno: None Declared, E. Leon: None Declared, M. Vendramini: None Declared, M. Levy Neto: None Declared, E. Bonfa: None Declared