The role of streptococcal hypersensitivity in the pathogenesis of Behçet's disease

Fumio Kaneko, Noritaka Oyama, Hirokatsu Yanagihori, Emiko Isogai, Kenji Yokota, Keiji Oguma

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Behçet's disease (BD) is still considered as a mysterious multisystemic disorder characterized by recurrent involvement of muco-cutaneous, ocular, intestinal, vascular and/or nervous system organs. In this review, we would like to highlight and discuss several important advances in our understanding of the pathogenesis of BD based on the intrinsic genetic factors including HLA-B51 and MICA expression and extrinsic triggering factors. As one of the extrinsic triggering factors, we focused on the hypersensitivity against oral streptococci which might be acquired through the innate immune mechanism. It was found that HLA-B51 restricted CD8 T cell response was clearly correlated with the target tissues expressing MICA*009 by stress in active BD patients with HLA-B51 as the intrinsic factors. Bes-1 gene and HSP-65 derived from oral S. sanguinis, which is the uncommon serotype (KTH-1, strain BD113-20), are supposed to play important roles as an extrinsic factor in BD pathogenesis. The peptides of the Bes-1 gene are highly homologous with the retinal protein Brn3b and moreover, the Bes-1 peptides were homologous with HSP-65 derived from microorganisms in association with the counterpart human HSP-60, which appeared reactively in the patients. HSP-65/60 also has high homologies with the respective T cell epitope of BD patients. Although HSP-65/60 and the peptides of Bes-1 gene were found to stimulate PBMCs from BD patients in the production of pro-inflammatory Th1 type cytokines, some homologous peptides of HSP-65 with T cell epitopes were found to reduce IL-8, IL-12 and TNF-α produced from PBMCs of active BD patients. The findings might be correlated with the clinically therapeutic effects for BD patients with severe uveitis, who were led to immunotolerance by the peptide of human HSP-60 (336-351), as previously reported. Then, the pathogenesis of BD was discussed referring to intrinsic genetic factors an extrinsic triggering factors in aspects of streptococcal hypersensitivity, which might be acquired through the innate immune mechanisms. The BD symptoms were thought to be due to vascular reactions as immune responses in correlation with monocyte expressed streptococcal agents.

Original languageEnglish
Pages (from-to)489-498
Number of pages10
JournalEuropean Journal of Dermatology
Volume18
Issue number5
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Hypersensitivity
HLA-B51 Antigen
Intrinsic Factor
Peptides
T-Lymphocyte Epitopes
Blood Vessels
Genes
Uveitis
Therapeutic Uses
Interleukin-12
Streptococcus
Interleukin-8
Nervous System
Monocytes
Cytokines
T-Lymphocytes
Skin

Keywords

  • Behçet's disease
  • Bes-1 gene
  • Heat shock protein
  • Streptococcus sanguinis
  • Vascular reaction

ASJC Scopus subject areas

  • Dermatology

Cite this

The role of streptococcal hypersensitivity in the pathogenesis of Behçet's disease. / Kaneko, Fumio; Oyama, Noritaka; Yanagihori, Hirokatsu; Isogai, Emiko; Yokota, Kenji; Oguma, Keiji.

In: European Journal of Dermatology, Vol. 18, No. 5, 09.2008, p. 489-498.

Research output: Contribution to journalArticle

Kaneko, Fumio ; Oyama, Noritaka ; Yanagihori, Hirokatsu ; Isogai, Emiko ; Yokota, Kenji ; Oguma, Keiji. / The role of streptococcal hypersensitivity in the pathogenesis of Behçet's disease. In: European Journal of Dermatology. 2008 ; Vol. 18, No. 5. pp. 489-498.
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