ABSTRACT
Behçet’s disease (BD) is recognized as a systemic inflammatory disease of unknown etiology. The disease is not a chronic inflammatory disease, is rather recurrent attacks of acute inflammation and progressively deterioration. Previous reports have shown three major pathophysiologic changes in BD; excessive neutrophil functions, vascular injuries with thrombotic tendency, and autoimmune responses. Association of HLA-B51 with the disease suggests importance of genetic predisposition for the development of this disease. Many reports suggest intimate linkage of immunological abnormalities and neutrophil hyperfunction to the disease manifestations. HLA-B51 molecules alone may be partly responsible for neutrophil hyperfunction in BD. Low levels of prostacycline and increased levels of von Willebrand factor in patients’ sera, and increased production of oxygen metabolites by their endothelium, may indicate endothelial cell damage in BD. Recent demonstration of enhanced responsiveness of BD patient T lymphocytes to 60 kDa human-derived heat shock protein (HSP) suggests that this response may reflect crossreaction between human-derived HSP and HSP from microbial causative agents. We therefore propose a working hypothesis for the etiopathogenesis of BD: In a genetically susceptible individual, an exogenous antigen such as a streptococcal or a viral antigen, of which HSP shares in an epitope with human-derived HSP, may stimulate HSP-specific T lymphocytes in addition to monocytes, and subsequently induce production of Th1 cytokines, IL-8, TNF, and IL-6. These cytokines stimulate monocytes and lymphocytes in an autocrine/paracrine fashion, and stimulate the vascular endothelium as well. Stimulation of polymorphonuclear cells by these cytokines also is of a particular importance for the pathogenesis of BD because of a genetic hyperresponsiveness of the polymorphonuclear cells in BD. The final outcome will be systemic vascular damage leading to various clinical manifestations of the disease.
