New Perspective on Behĉet's Disease

Abstract

There are many distinct differences between Behçet's disease of Silk Route and that of outside Silk Route; genetic factors, role of neutrophils, and severity of this disease. We have thus emphasized that we prefer the term “Behçet's syndrome” rather than “Behçet's disease”. In this chapter, Behçet's disease seen along the Silk Route will be mainly discussed.

HLA-B51 molecules themselves may be responsible, at least in part, for the neutrophil hyperfunction in Behçet's disease; a significant correlation was observed between the neutrophil hyperfunction and the possession of HLA-B51 phenotype, regardless of the presence of the disease, in both humans and HLA-B transgenic mice.

T cells in this disease, proliferated vigorously in response to a specific peptide of human heat shock protein (HSP)-60; however, T cells from normal subjects'or patients with rheumatoid arthritis, did not. This peptide has the amino acid sequence of 336-351 of human HSP-60, which is similar, but not identical to specific peptide of mycobacterial HSP-65. We have further analyzed T cell receptor (TCR) usage of HSP-responsive T cells by means of TCR V/β subfamily specific monoclonal antibodies and polymerase chain reaction and single strand conformation polymorphism-based technique. We found that T cells with specific TCR Vβ subfamilies proliferated and increased in number in response to the peptide by an antigen-specific fashion. The result of recurrent exposure to the HSP may break the tolerance to self-HSP, and provoke T cell responses to self- and microbial-HSP. Such T cells produced Th1-like proinflammatory and/or inflammatory cytokines. This leads to tissue injury, possibly via delayed-type hypersensitivity reaction, macrophage activation, and activation and/or recruitment of neutrophils. Our data shed a new light on the autoimmune nature of Behçet's disease; a novel multistep molecular mimicry mechanisms may induce and/or exacerbate Behçet's disease by bacterial antigens that activate T cells previously educated by self-peptides of HSP. This would lead to positive selection of autoreactive T cells in this disease.

Key Words:

• Behçet's disease
• Behçet's syndrome
• Immunological abnormalities
• Neutrophil hyperfunction
• Autoimmune disease
• HLA-B51