Behcet's disease is recognized as a systemic inflammatory disease of unknown etiology. The disease has a chronic course with periodic exacerbations and progressive deterioration. Previous reports have shown at least three major pathophysiologic changes in Behcet's disease; excessive functions of neutrophils, vasculitis with endothelial injuries, and autoimmune responses. Many reports suggested that immunological abnormalities and neutrophil hyperfunction may be involved in the etiology and the pathophysiology of this disease. HLA-B51 molecules by themselves may be responsible, in part, for neutrophil hyperfunction in Behcet's disease. T cells in this disease proliferated vigorously in response to a specific peptide of human heat shock protein (hsp) 60 in an antigen-specific fashion. T cells reactive with self-peptides 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. These data shed new light on the autoimmune nature of Behcet's disease; molecular mimicry mechanisms may induce and/or exacerbate Behcet's disease by bacterial antigens that have activated T cells which are reactive with self-peptide(s) of hsp. This would lead to positive selection of autoreactive T cells in this disease.
Behcet's Syndrome/pathology ; Behcet's Syndrome/immunology* ; Behcet's Syndrome/etiology ; Chaperonin 60/immunology ; Eye/pathology ; Human ; Neutrophils/physiology ; Skin/pathology ; T-Lymphocytes/physiology

The presence of a lupus anticoagulant was evaluated in patients with Bechet's disease by the kaolin clotting time method. Four percents (three patients) of 69 patients analyzed were found positive for the lupus anticoagulant. However, no statistically significant association existed between the presence of this antibody and the presence of thrombosis, clinical activity, clinical type, antinuclear antibodies and the positive VDRL test.
Behcet Syndrome/*immunology ; Cardiolipins/immunology ; Female ; Human ; Lupus Coagulation Inhibitor/*analysis ; Male

Although the precise pathoetiology of Behcet's disease (BD) remains obscure, patients with BD have a high incidence of chronic infectious foci, indicating an enhanced susceptibility to chronic tonsillitis, and dental caries. Sometimes, clinical symptoms appear after treatment of these foci in BD patients. It is believed that BD might be related to an allergic reaction to a bacterial infection in view of the many clinical symptoms, especially the presence of aphthous and genital ulcerations. An attempt to obtain cutaneous responses to bacterial antigens has been carried out using various vaccines developed from bacteria isolated from the ulcerative lesions and oral cavities of BD patients. BD patients often show intense hypersensitivity to various strains of streptococci, not only by their cutaneous reactions but also by in vitro testing. In this report, we describe our previous studies on the correlation between streptococcal antigens and the pathogenesis of BD and also discuss the recent reports of other authors. The intense hypersensitivity to streptococcal antigens acquired after streptococcal infection is thought to play an important role in the appearance of symptoms in BD patients since the production of pro-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) was enhanced when stimulated with streptococcal antigen in a culture system. Minocycline, an antibiotic to which certain strains of streptococci are sensitive, reduced the frequency of clinical symptoms in BD patients as well as the production of pro-inflammatory cytokines by BD-PBMC stimulated with streptococcal antigen.
Adult ; Antibiotics, Tetracycline/therapeutic use* ; Antigens, Bacterial/immunology ; Behcet's Syndrome/immunology ; Behcet's Syndrome/etiology* ; Behcet's Syndrome/drug therapy ; Cytokines/biosynthesis ; Female ; Human ; Male ; Minocycline/therapeutic use* ; Skin Tests ; Streptococcal Infections/drug therapy ; Streptococcal Infections/complications*

Behcet's disease is a chronic relapsing multisystemic inflammatory disorder characterized by four major symptoms (oral aphthous ulcers, genital ulcers, skin lesions, and ocular lesions) and occasionally by five minor symptoms (arthritis, gastrointestinal ulcers, epididymitis, vascular lesions, and central nervous system symptoms). Although the etiology of Behcet's disease is still unknown, there have been recent advances in immunopathogenic studies, genome-wide association studies, animal models, diagnostic markers, and new biological agents. These advances have improved the clinical understanding of Behcet's disease and have enabled us to develop new treatment strategies for this intractable disease, which remains one of the leading causes of blindness.
Animals ; *Behcet Syndrome/epidemiology/immunology/therapy ; Biological Therapy/*trends ; Disease Models, Animal ; Humans ; Prevalence ; *World Health

Antiendothelial cell antibodies (AECA) have been detected in the sera of patients of autoimmune diseases showing vasculitis. Using IgM-ELISA, we found AECA in 42 (56%) of 75 sera samples from patients with Behcet's disease in a previous study. All of the 15 AECA-positive sera of Behcet's disease patients had an increased expression of the intercellular cell adhesion molecule-1 (ICAM-1), 93.3% of the sera induced the vascular cell adhesion molecule-1 (VCAM-1), and 100% of the serum induced the E-selectin molecule on human dermal microvascular endothelial cells (HDMEC). After stimulation of HDMEC with AECA-positive sera of Behcet's disease patients, the expression of ICAM-1 and VCAM-1 on HDMEC increased significantly at 4 hours, reaching a peak at 16 hours. Expression of E-selectin was induced at 1 hour after stimulation with a peak at 4 hours and it decreased thereafter. Adherence of T lymphocytes to HDMEC increased significantly after stimulation with AECA-positive sera from Behcet's disease patients. Also, the adherence of T lymphocytes to HDMEC increased at 4 hours and returned to its normal level at 48 hours. These results show that AECA-positive sera of Behcet's disease patients are capable of activating HDMEC to promote the adherence of T lymphocytes to increase the expression of ICAM-1, VCAM-1, and E-selectin on the cell surfaces. The whole process may play an important role in the pathogenesis of vasculitis in Behcet's disease.
Antibodies/physiology* ; Antibodies/blood ; Behcet's Syndrome/immunology ; Behcet's Syndrome/blood* ; Blood Physiology ; Cell Adhesion/physiology ; Cells, Cultured ; Endothelium, Vascular/physiology* ; Endothelium, Vascular/immunology* ; Endothelium, Vascular/cytology ; Human ; Microcirculation/physiology ; Skin/blood supply* ; T-Lymphocytes/physiology*

Behcet's disease is a chronic multi-systemic disease of unknown origin that includes mucocutaneous, ocular, cardiac, vascular, renal, gastrointestinal, neurologic and cutaneous involvement. The disease is spread throughout the world, but it is most prevalent in the eastern Mediterranean region-along the Silk Road-, and in Japan, China, and Korea. Recently, we treated a Mongolian patient who had complete-type Behcet's disease. As far as we know, this case is the first report of a Mongolian with Behcet's disease in the English literature. HLA typing in this patient revealed A2, A24; B51, B35; Cw4, Cw7; DR9, DR11. Study of the MICA genetype showed *5, *6 positive. Our data provided adequate evidence, from an epidemiological aspect, to support the belief that Behcet's disease is most prevalent along the old Silk Road.
Adult ; Alleles ; Behcet Syndrome/*genetics/immunology ; Genotype ; HLA-B Antigens/*genetics ; Histocompatibility Antigens Class I/*genetics ; Human ; Male

Fifty-two Korean patients with Behcet's syndome were typed for HLA antigens. 52 apparently healthy Korean subjects were used as controls; 42 for HLA-A, B, C and all 52 for HLA-DR typing. HLA-B5 and DRw8 presented significantly high frequencies in all patiens. According to Shimizu's classification, HLA-B5 and DRw8 were significantly increased in the complete type; B5 in the incomplete type; DR3 in the suspected-possible type. According to Lehner's classification, HLA-DR3 was significantly increased in the neurological type; B5 in the ocular type; B5 in the ocular type. We confirmed the association of HLA-B5 with the severity of Beh et's syndrome. A relation might exist between DRw8, DR3 and Behcet's syndrome.
Adolescent ; Adult ; Behcet Syndrome/*immunology ; Female ; HLA Antigens/*analysis/classification ; Human ; Korea ; Male ; Middle Age ; Support, Non-U.S. Gov't

To know the prognosis of Behcet's disease with HLA-Bw 51 antigen, comparison studies of 24 cases of Behcet's disease were investigated. The sex distribution was 14 males (58%) and 10 females (42%). The patients were grouped into three clinical types: the complete type with 11 cases (45%), the incomplete type with eight cases (33%) and the suspect type with five cases (22%), according to the criteria established by the Behcet's Disease Research Committee in Japan (1982). They were also divided into three ocular types according to the location of the inflammation: the anterior segment type, the fundus type and the mixed type. They were divided into 10%, 10% and 60% in HLA-Bw 51 negative group and 14%, 22% and 64% in HLA-Bw 51 positive group, respectively. Skin lesions observed in 30% of the HLA-Bw 51 negative group and 70% of the HLA-Bw 51 positive group, which was statistically significant (p < 0.01). The other general symptoms and the visual acuity between the two groups were not statistically significant (p > 0.1).
Adolescent ; Adult ; Behcet Syndrome/classification/*complications/immunology ; Eye Diseases/*etiology/immunology ; Female ; HLA-B Antigens/*analysis ; HLA-B51 Antigen ; Humans ; Male ; Middle Aged ; Prognosis ; Visual Acuity

We tested 59 Greek patients with Behcet's Disease (BD) for serum anti-Saccharomyces cerevisiae antibodies. No increase of these antibodies was detected in the cases compared to 55 healthy unrelated blood donors from the same population. This finding is in contrast with the correlation between Saccharomyces cerevisiae antibodies and BD as reported in other populations. It seems that environmental factors may contribute to disease expression in different populations, producing different effects according to the individual's genetic predisposition. Saccharomyces cerevisiae antibodies do not seem to be of any significance in the Greek population.
Adolescent ; Adult ; Aged ; Antibodies, Fungal/*immunology ; Behcet Syndrome/*immunology/microbiology ; Case-Control Studies ; Female ; Greece ; Humans ; Immunoglobulin A/immunology ; Immunoglobulin G/immunology ; Male ; Middle Aged ; Saccharomyces cerevisiae/*immunology ; Young Adult

Behcet's disease (BD) is a multisystemic chronic inflammatory disease. It is characterized by recurrent oral and genital ulcers, uveitis, skin lesions and other manifestations, including neurologic, vascular, joint, and gastrointestinal ulcers of variable severity. Recurrent aphthous ulcer (RAU) represents a very common, but poorly understood, mucosal disorder. If a patient of RAU without any other typical symptoms of BD has gastrointestinal symptoms, it is difficult to distinguish this RAU from true BD with gastrointestinal involvement. Because pathognomonic clinical features and tools are absent, the differential diagnosis of these two diseases relies on the characteristic clinical features and the judgement of an experienced physician. Sixty-five out of a total 960 RAU patients and forty-four of 556 BD patients with gastrointestinal symptoms between January 1996 and December 2003 participated in this study. All were evaluated with esophagogastroduodenoscopy and colonoscopy. Clinical, endoscopic and histopathologic findings were analyzed and ELISA tests were conducted to detect serum levels of ASCA and pANCA. No significant difference was found between the two groups. Differential diagnosis between RAU with gastrointestinal symptoms and BD with gastrointestinal involvement requires further prospective, large-scale study.
Adolescent ; Adult ; Aged ; Antibodies, Antineutrophil Cytoplasmic/blood ; Antibodies, Fungal/blood ; Behcet Syndrome/*diagnosis/immunology/pathology ; Comparative Study ; Diagnosis, Differential ; Endoscopy ; Female ; Gastrointestinal Diseases/*diagnosis/immunology/pathology ; Humans ; Male ; Middle Aged ; Saccharomyces cerevisiae/immunology ; Serologic Tests ; Stomatitis, Aphthous/*diagnosis/immunology/pathology