Cross-reaction between the major epitope of Ro60 protein (pep216–232) and a homologous peptide of Coxsackievirus 3C protease

Background

Coxsackievirus RNA has recently been detected in biopsy specimens of minor salivary glands from patients with Sjögren's syndrome (SS). A peptide of 3C protease of Coxsackievirus (pepCoxs) has 87% homology with a major linear B-cell epitope of Ro60 protein spanning the sequence 216–232aa.

Objective

To investigate a possible cross-reaction between Coxsackievirus 3C protease and Ro60 autoantigen.

Methods

PepCoxs MVTSTITEKLLKNLVKI and pep216–232 of Ro60 KALSVETEKLLKYLEAV were prepared. Sera from 27 patients with SS and 28 patients with systemic lupus erythematosus (SLE) were tested against the two homologous peptides. Twenty-eight samples were a-Ro (+), and 26 samples were a-Ro/a-La (+). Sera from 27 healthy individuals were used as normal controls. Antibodies against Ro60 peptide were purified and tested for antipeptide reactivity.

Results

Of SLE sera 25%, and 33.3% of SS sera reacted against pep216–232, whereas 28% of SLE sera and 37% of SS sera reacted against pepCoxs. The reactivity of normal sera against pep216–232 and pepCoxs was 17.4% and 3.7%, respectively. Pep216–232 was recognized by 17% of the a-Ro (+) sera and by 42% of the a-Ro/La (+) sera, whereas pepCoxs was recognized by 28.5% and 38% of the a-Ro (+) and a-Ro/La (+) sera, respectively. Both peptides reacted more prominently with a-Ro/La (+) sera from SS patients. Purified a-Ro60 antibodies reacted with both peptides and inhibition experiments revealed the specificity of this reaction.

Conclusion

These results revealed a possible cross-reaction between the major linear B-cell epitope of Ro60 protein (216–232aa) and the homologous peptide of Coxsackie virus 3C-protease in SS patients. This cross-reaction might potentially play a role on autoantibody formation and pathogenesis of SS.