Behcet’s Disease and Related Diseases -Immune Reactions to Oralstreptococci in Their Pathogenesis

Fumio Kaneko, Ari Togashi, Erika Nomura, Koichiro Nakamura

Abstract


Behçet’s disease (BD) is a systemic disorder characterized by the recurrent involvement in the muco-cutaneous, ocular, intestinal, vascular, and/or nervous system organs. The clinical muco-cutaneous manifestations including recurrent aphthous stomatitis (RAS), erythema nodosum (EN) –like eruption, genital ulceration, etc. of patients with BD were reviewed in their pathogenesis comparing with the similar symptoms seen in patients without BD (non-BD). Most of BD patients tend to have hypersensitivity against streptococci which might be acquired in the oral cavity through the innate immune mechanism. Generally, BD patients have the systemic symptoms following RAS symptom as an immune reaction. Then, the characteristics of hypersensitivity to oral streptococci may be utilized in order to make a diagnosis for BD. The skin prick with self-saliva including oral streptococci was much more sensitive than “Pathergy test” conventionally used for BD diagnosis. HLA-B51-restricted CD8+ T cell response is suspected to catch the target tissues expressing major histocompatibility complex class 1 chain-related gene A (MICA) by stress in active BD patients. Bes-1 gene and 65kD of heat shock protein (HSP-65) derived from Streptococcus sanguinis (S. sanguinis) are detectable in the lesions. The peptides of Bes-1 gene are highly homologous with the retinal protein Brn3b which might be connected with the eye involvement in BD patients. Also, the peptides seem to be homologous with HSP-65 in association with the human HSP-60 which reactively appeared in serum of the patients involved by S. sanguinis. Then, the pathogenesis of BD was conclusively discussed on the relationship between RAS and the systemic symptoms by the vascular reaction due to immune responses against antigens derived from S. sanguinis. Non-BD patients with RAS and/or Lipschutz genital ulceration were weekly sensitized by oral streptococci, except for patients with EN.

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