Serum IgA reactivity against GroEL of Streptococcus sanguinis and human heterogeneous nuclear ribonucleoprotein A2/B1 in patients with Behçet disease

Abstract

BACKGROUND: Infectious agents, especially Streptococcus sanguinis and herpes simplex virus, have long been postulated as major triggering factors for Behçet disease (BD). OBJECTIVES: To identify an anti-S. sanguinis antigen reacting with serum IgA antibody in patients with BD. METHODS: We detected a target protein by proteomics analysis and evaluated serum IgA reactivity of 100 patients with BD against the identified streptococcal target protein and human heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1. Homologous epitope sequences between the streptococcal target protein and human hnRNP A2/B1 were also evaluated. RESULTS: Four protein bands were detected by immunoprecipitation, and chaperonin GroEL was identified by a proteomics analysis. Reactivity of serum IgA against recombinant S. sanguinis GroEL was detected in 77 of 100 patients with BD (77%) and in 21 of 70 healthy controls (30%). In addition, reactivity of serum IgA against human recombinant hnRNP A2/B1 was seen in 79 of 100 patients with BD (79%) and in eight of 70 healthy controls (11%). Among the eight distinctive epitopes with significant homology between S. sanguinis GroEL and human hnRNP A2/B1, the serum IgA reactivity of patients with BD was markedly higher with epitope 3 (hnRNP A2/B1 peptide 33-46 and GroEL peptide 57-70) and epitope 6 (hnRNP A2/B1 peptide 177-188 and GroEL peptide 347-358). CONCLUSION: We identified an S. sanguinis GroEL protein as a target of serum anti-S. sanguinis IgA antibody reactivity in patients with BD. In addition, patients with BD exhibited serum IgA reactivity against homologous epitope regions between S. sanguinis GroEL and human hnRNP A2/B1.