Evidence for coxsackievirus infection in primary Sjögren's syndrome

Arthritis Rheum. 2004 Sep;50(9):2897-902. doi: 10.1002/art.20463.


Objective: Primary Sjögren's syndrome (SS) is an autoimmune disease characterized by activation of minor salivary gland (MSG) epithelial cells and B and T lymphocytic infiltrates. These findings have long encouraged the hypothesis that a persistent viral infection of the MSG epithelial cells may drive the autoimmune response; however, the identity of that virus has remained elusive. The aim of this study was to test this hypothesis.

Methods: We applied the differential display protocol to MSG RNA samples from patients with primary SS and healthy controls. We then used seminested reverse transcriptase-polymerase chain reaction to amplify the 5'-noncoding region (5'-NCR) of the enteroviral genome in 8 patients with primary SS, 9 patients with secondary SS, and 8 control subjects. Immunohistochemistry was performed to study the expression of the VP1 enteroviral capsid protein in MSG biopsy samples from 12 patients with primary SS, 8 patients with secondary SS, and 16 controls.

Results: Differential display analysis yielded a 94-bp fragment of coxsackievirus B4 (CVB4) P2A gene in the primary SS samples. The 5'-NCR was amplified in 7 samples from patients with primary SS and in no samples from patients with secondary SS or controls. The 7 amplified products were sequenced; 4 of the sequences were found to be 98-99% identical to the 5'- NCR of CVB4, and 3 were found to be 97-98% identical to the 5'-NCR of CVA13. Immunohistochemistry for the enteroviral capsid protein VP1 revealed positive staining in epithelial cells and lymphocytic infiltrates in 11 primary SS samples, 1 secondary SS sample, and no control samples.

Conclusion: We provide evidence that primary SS may be associated with coxsackievirus infection of the MSG epithelial cells and focal lymphocytic infiltrates. Our findings are formulated in a hypothesis concerning the possible role of coxsackieviruses in the induction and maintenance of autoimmunity in primary SS.

MeSH terms

  • Coxsackievirus Infections / immunology*
  • Coxsackievirus Infections / virology
  • Enterovirus B, Human / isolation & purification*
  • Epithelial Cells / immunology
  • Epithelial Cells / virology
  • Female
  • Humans
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Salivary Glands, Minor / immunology
  • Salivary Glands, Minor / virology*
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / virology*