Infection may trigger this condition, activating autoreactive lymphocytes to respond not only to the infecting entity but also to hnRNP-A2/B1 proteins.

Behçet disease (BD) is a chronic multisystem disease that often involves vasculitis and thromboses; these manifestations suggest that the immune system may be targeting autoantigens in the endothelial cells. Indeed, antibodies reacting with endothelial cell substrates occur in the sera of patients with BD. Often, the mouths of patients with BD are colonized by Streptococcus sanguis, and intradermal skin tests with streptococcal antigens often elicit strong delayed hypersensitivity reactions, suggesting that infectious agents may play an etiopathologic role.


Investigators performed Western blot testing to define which antigen was reacting with the antiendothelial cell antibody in patients with BD. Of 30 BD patients, 25 had serum IgA antibodies reacting with hnRNP-A2/B1 proteins; hnRNP proteins bind to mRNA. All patients with the IgA autoantibodies had mouth ulcers, and some had other involvement: genital ulcers (84%), skin disease (84%), ocular disease (64%), articular disease (36%), gastrointestinal tract disease (16%), vascular disease (8%), and neurologic disease (4%). Using an ELISA assay, the investigators also found IgA antibodies reacting with recombinant streptococcal heat-shock protein 65 (hsp-65), which shares homology with human hsp-60. The authors suggest that infection, especially with S. sanguis, triggers BD, activating the autoreactive lymphocytes to react not only with streptococcal hsp-65 but also with cross-reacting human hnRNP-A2/B1.


Citation(s):

Cho SB et al. Identification of hnRNP-A2/B1 as a target antigen of anti-endothelial cell IgA antibody in Behçet's disease. J Invest Dermatol 2012 Mar; 132:601.