EBV reactivation serological profile in primary Sjögren's syndrome: an underlying trigger of active articular involvement?

Rheumatol Int. 2013 May;33(5):1149-57. doi: 10.1007/s00296-012-2504-3. Epub 2012 Sep 6.

Abstract

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. 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). Antibodies to EBV (anti-VCA IgG/IgM, anti-EBNA-1 IgG, anti-EA-D IgG) were determined by ELISA. 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). Anti-VCA IgM was negative in all cases. Noteworthy, higher frequency and increased mean levels of anti-EA-D were observed 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). Further analysis of patients with (n = 36) and without (n = 64) anti-EA-D revealed comparable age/gender/ethnicity (p ≥ 0.551), current prednisone dose (4.8 ± 6.9 vs. 5.1 ± 10.4 mg/day, p = 0.319), and 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 was more frequent (25 vs. 9.4 %, p = 0.045) in anti-EA-D positive patients. Anti-EA-D antibodies were not associated with anti-Ro/SSA (p = 1.000), anti-La/SSB (p = 0.652), rheumatoid factor (p = 1.000), anti-α-fodrin (p = 0.390) or antiphospholipid antibodies (p = 0.573), not suggesting cross-reactivity. The higher anti-EA-D frequency associated with joint activity raises the possibility that a subclinical EBV reactivation may trigger or perpetuate the articular involvement in pSS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Antinuclear / blood
  • Antibodies, Viral / blood
  • Antigens, Viral / immunology*
  • Biomarkers / blood
  • Case-Control Studies
  • Chi-Square Distribution
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glucocorticoids / therapeutic use
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Immunosuppressive Agents / therapeutic use
  • Joints / drug effects
  • Joints / immunology*
  • Joints / virology*
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Risk Factors
  • Severity of Illness Index
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / drug therapy
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / virology*
  • Virus Activation*

Substances

  • Antibodies, Antinuclear
  • Antibodies, Viral
  • Antigens, Viral
  • Biomarkers
  • Epstein-Barr virus early antigen diffuse component
  • Glucocorticoids
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunosuppressive Agents
  • Prednisone