OBJECTIVES: To evaluate the potential of HLA as a candidate gene for the genetic marker of bipolar disorder, we carried out the association study between allelic frequency of HLA and bipolar disorder. METHODS: HLA class I and class II allelic frequencies were assessed in 87 Korean bipolar disorder patients and were compared with the data from 206 normal controls. HLA class I typing was performed with microlymphocytotoxicity method and HLA class II(DQB1 and DRB1) genotyping with reverse dot hybridization. The allelic frequencies were analyzed using x2 test with two-tailed Fisher's exact test. RESULTS: Bipolar disorder patients showed increased allelic frequencies of HLA-A29 and B54 and decreased allelic frequencies of HLA-B51 and DRB1*02 compared to normal controls. CONCLUSION: These results suggest the possibility of association between HLA gene and bipolar disorder. To clarify the genetic influences of HLA on bipolar disorder, further systematic studies should be conducted.
Alleles* ; Bipolar Disorder* ; Genetic Markers ; HLA-B51 Antigen ; Humans

Behcet's disease (BD) is a chronic inflammatory disorder of unknown cause, characterized by recurrent oral ulcerations, genital ulcerations, ocular and skin lesions. Although the exact pathogenesis for BD is not completely understood, it has been suggested that the disease is triggered in genetically susceptible individuals by environmental factors, such as microbial agents. It is noted that multiple genes, including MHC and non-MHC genes, are implicated in the pathogenesis of BD. Although the HLA-B51 is known to be the candidate gene showing the strongest association with BD, it is necessary to be determined whether this HLA molecule is directly involved in the pathogenesis of BD. Cross-reactivity between microbial 65-kD and human 60-kD heat shock proteins is demonstrated to cause an increased T cell (particularly gammadelta T cell) response. The resultant overexpression of pro-inflammatory cytokines (mainly Th-1 type) from several immune cells seems to be responsible for the enhanced inflammatory reaction, and this may be associated with the genetic factors.
Cytokines ; Heat-Shock Proteins ; HLA-B51 Antigen ; Humans ; Oral Ulcer ; Skin ; Ulcer

BACKGROUND/AIMS: There is controversy related to the role of smoking in affecting the clinical features of patients with Behcet's disease (BD). The aim of this study was to investigate the effect of smoking on clinical manifestations in Korean BD patients. METHODS: We enrolled 131 patients with BD who fulfilled the International Study Group (ISG) criteria of 1990. The disease-related clinical features of BD-oral ulcers, genital ulcers, ocular lesions, arthritis, vascular lesions, gastrointestinal lesions-and central nerve lesions, smoking history, disease duration, and the presence of HLA-B51 were retrospectively assessed through medical record reviews and patient interviews. Statistical analysis was performed using Chi-square, Fisher's exact, or student t-test, if appropriate. RESULTS: The frequencies of vascular and gastrointestinal lesions in smokers were significantly increased compared to those in non-smokers (p=0.040, OR=3.341, 95% CI 1.083-10.305; p=0.012, OR=3.878, 95% CI 1.379-10.906, respectively). Male smokers developed vascular lesions more frequently compared to female smokers, male non-smokers, and female non-smokers (p=0.025, OR=3.896, 95% CI 1.245-12.196). Moreover, smoking, male sex, and positive HLA-B51 may be risk factors for the development of gastrointestinal lesions in BD. Venous lesions were more frequently found in male smokers compared with other patients (p=0.038). CONCLUSIONS: Smoking may be associated with the development of vascular and gastrointestinal lesions in Korean BD patients. A large population prospective assessment of the clinical effect of smoking on BD is needed.
Arthritis ; Female ; HLA-B51 Antigen ; Humans ; Male ; Medical Records ; Retrospective Studies ; Risk Factors ; Smoke ; Smoking ; Ulcer

In order to evaluate association of particular HLA typing with certain uveitis in Korean population, HLA antigens were analyzed in 114 uneitis patients(acute anterior uveitis: 32 cases, Behcet`s disease: 25 cases, intermediate uveitis: 19 cases, Vogt-Koyanagi-Harada (V-K-H) syndrome: 10 cases, retinal vasculitis: 12 cases, Eale`s disease: 3 cases, posterior uveitis: 9 cases, pan.uveitis: 4 cases). The stronger association between acute anterior uveitis and HLA-B27 was statistically significant, and this result was similar to reports in other ethnic groups. Also, the association between V-K-H syndrome and HLA-DR4 showed same results. But the high frequency of HLA-DR7 in the patients with V-K-H syndrome was unque in patients of Korean popjlation and statistically significant. The association between HLA-A2 and posterior uveitis was high in patients of Korean population and statistically significant. Behcet`s disease was stronger association with HLA-B51 but not statistically significant and much weaker association than reports in Japanese group. Although many similarities of associations between particular uveitis and HLA typing were detected as compared with other ethnic groups, distinctive HLA associations were demonstrated in Korean population. Additional cases and long-term follow-up are required to confirm the association with HLA typing and the relationship with prognosis including clinical and laboratory variabilities.
Asian Continental Ancestry Group ; Ethnic Groups ; Follow-Up Studies ; Histocompatibility Testing ; HLA Antigens ; HLA-A2 Antigen ; HLA-B27 Antigen ; HLA-B51 Antigen ; HLA-DR4 Antigen ; HLA-DR7 Antigen ; Humans ; Prognosis ; Retinal Vasculitis ; Uveitis* ; Uveitis, Anterior ; Uveitis, Intermediate ; Uveitis, Posterior

OBJECTIVE: Behcet? disease (BD) is a chronic inflammatory disorder affecting several organs. The etiology of BD remains unclear, although genetic factors, infectious agents, and immune mechanisms have been studied. The association of BD with certain genetic factors, especially HLA-B51 antigen, is well known in some geographical areas. Nevertheless, the familial occurrence of BD is rare. In this paper, HLA phenotype was evaluated in one family member showing the clustering of BD. METHODS: The serological tissue typing of HLA class I and class II antigens was performed by standard National Institutes of Health microlymphocytotoxicity method in seven family members in which four siblings were affected by BD. The diagnosis of BD was established by the criteria of the International Study Group of BD in these four siblings. RESULTS: In this family study, all members had HLA-A2 and DQ3 antigens. Although HLA-B51 antigen was positive in six out of seven family members, BD was developed in three of the six having HLA-B51 antigen. Three siblings had the exact same HLA phenotype. However, only one person had BD among three siblings with identical HLA phenotype. In addition, all siblings who developed erythema nodosum-like lesion had HLA-B51 antigen. CONCLUSION: This family suggests that the familial clustering of BD may not be explained solely by a susceptible HLA phenotype. The environmental factor or other genetic factors besides HLA-B51 might play a role in the development of BD. Furthermore, more studies and information will be needed to clarify the role of A2 and DQ3 antigens in BD.
Diagnosis ; Erythema ; Histocompatibility Antigens Class II ; Histocompatibility Testing ; HLA Antigens* ; HLA-A2 Antigen ; HLA-B51 Antigen ; Humans ; National Institutes of Health (U.S.) ; Phenotype ; Siblings

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

BACKGROUND/AIMS: The clinical manifestations of Behcet disease (BD) have been reported to differ according to country, region, and race. Gender, onset age, and human leukocyte antigen (HLA)-B51 have also been known as the factors that influence the clinical features of BD. The aim of this study is to investigate the clinical phenotypes of Korean patients who visited the rheumatology clinic with BD with respect to gender, onset age, and HLA-B51. METHODS: Total 193 Korean patients (129 females and 64 males) fulfilling the international criteria for BD were retrospectively assessed. RESULTS: The mean age at disease onset and disease duration of the BD patients were 32.2 ± 11.1 and 14.2 ± 9.3 years, retrospectively. Females suffered more frequently from genital ulcers (90.7% vs. 75.0%, p < 0.01), peripheral arthritis (67.4% vs. 43.8%, p < 0.01), and inf lammatory low back pain (38.8% vs. 23.4%, p = 0.03) than males, while skin involvement was more frequent in males than in females (90.6% vs. 75.2%, p = 0.01). The patients with late onset of BD (> 40 years) suffered from neurologic involvement (15.9% vs. 4.2%, p = 0.007) more frequently than those with early onset of BD. The patients with HLA-B51 showed earlier onset of disease than without HLA-B51 (28.3 ± 11.4 years vs. 33.8±11.6 years, p = 0.02) and the neurologic and gastrointestinal involvements were more frequent in the patients without HLA-B51 than with HLA-B51 (17.2% vs. 2.5%, p = 0.02 and 20.7% vs. 2.5%, p = 0.01, respectively). CONCLUSIONS: The clinical phenotypes in Korean patients with BD may be influenced by gender, onset age and HLA-B51.
Age of Onset* ; Arthritis ; Behcet Syndrome* ; Continental Population Groups ; Female ; Gender Identity ; HLA-B51 Antigen* ; Humans ; Leukocytes ; Low Back Pain ; Male ; Phenotype* ; Retrospective Studies ; Rheumatology ; Skin ; Ulcer

We report the case of a 5-year-old male patient with multiple aseptic splenic abscesses associated with Behçet's disease. The patient visited Gachon University Gil Hospital with fever, abdominal pain, and acute watery and bloody diarrhea, and reported a 2-year history of chronic abdominal pain and intermittent watery diarrhea. He was treated with antibiotics at a local clinic for fever and cervical lymph node swelling. Additionally, he had recurrent stomatitis. A colonoscopy showed multiple well-demarcated ulcerations throughout the colon, and abdominal computed tomography showed multiple splenic abscesses. Pathergy and HLA-B51 tests were positive. Investigations did not reveal any infectious organisms in the aspirate obtained via ultrasound-guided fine needle aspiration. After steroid treatment, all symptoms and multiple aseptic splenic abscesses resolved. However, oral ulcers, genital ulcers, and abdominal pain recurred after tapering the steroids. Infliximab treatment improved the patient's symptoms. However, 5 months after the treatment, the symptoms recurred. The treatment was changed to include adalimumab. Subsequently, the patient's symptoms resolved and colonoscopic findings improved. No recurrence was noted after 3 months of follow-up.
Abdominal Pain ; Abscess* ; Adalimumab ; Anti-Bacterial Agents ; Behcet Syndrome ; Biopsy, Fine-Needle ; Child* ; Child, Preschool ; Colon ; Colonoscopy ; Diarrhea ; Fever ; Follow-Up Studies ; HLA-B51 Antigen ; Humans ; Infliximab ; Lymph Nodes ; Male ; Oral Ulcer ; Pediatrics ; Recurrence ; Spleen ; Steroids ; Stomatitis ; Ulcer

Central nervous system involvement of Behcet's disease (BD) shows various neuropsychiatric manifestations. The differential diagnosis may include many other systemic or neurologic diseases. Moyamoya disease (MD) is a progressive cerebrovascular occlusive disease of unknown etiology with a high incidence in Korea and Japan. HLA-B51 is significantly associated with both MD and BD. We first report a case of BD associated with MD in a 32-year-old woman with transient ischemic attacks of left hemiparesis and episodic dizziness. She was diagnosed as having BD manifested with oral ulcer, genital ulcer, erythema nodosum and positivity of pathergy reaction and HLA-B51. There was no evidence of cerebral infarction or hemorrhage in brain MRI. MR angiogram and 4-vessel angiography showed occlusion of bilateral internal carotid arteries and the development of collateral circulation, suggestive of MD. Bypass surgery was successfully performed. When evaluating the manifestations of MD, a chronic inflammatory disease, such as BD, needs to be considered as the underlying disease, especially in prevalent area of both diseases.
Adult ; Angiography ; Brain ; Carotid Artery, Internal ; Central Nervous System ; Cerebral Infarction ; Collateral Circulation ; Diagnosis, Differential ; Dizziness ; Erythema Nodosum ; Female ; Hemorrhage ; HLA-B51 Antigen ; Humans ; Incidence ; Ischemic Attack, Transient ; Japan ; Korea ; Magnetic Resonance Imaging ; Moyamoya Disease* ; Oral Ulcer ; Paresis ; Ulcer