PURPOSE: Immune pathophysiology of aplastic anemia (AA) has been indirectly inferred from responses to immunosuppressive agents. An association between AA and HLA-A2, or HLA-DR2 (its serologic split, HLA-DR15; or its molecular correspondents, DRB1*1501) has been implicated. The presence of HLA-DR15 (including DR2 or DRB1*15) has been closely associated with a favorable response to immunosuppression in AA. This study was aimed to characterize Korean patients with AA by determining the association with certain HLA alleles, such as HLA-DR2 or HLA-A2, and their implications in terms of the response to immunosuppression. METHODS: One-hundred eighteen children with AA from 10 university hospitals between 1990 and 2001 were enrolled in this multicenter, retrospective study. Among them, HLA data were available from 80 patients. Tests of proportions were used to compare allelic frequencies. RESULTS: The frequency of HLA-A2 (58.8%) or HLA-DR2 (24.7%) in AA was not significantly different from those of the controls. Analysis of the patients treated with immunosuppression (N=86) showed that, 50.0% of patients showed a response, including 16.0% of complete response at 6 months. The presence of DR2 allele did not portend a favorable response to immunosuppressive therapy. CONCLUSION: Unlike Western countries, the association of AA with certain HLA alleles was not documented in the Korean population. Moreover, the presence of HLA-DR2 did not predict a favorable response to immunosuppression. This peculiar characteristics of Korean AA needs to be investigated whether these findings reflect ethnic differences, different contribution of immune-mediated AA, different immune mechanisms, or mere limitation by number of study patients.
Alleles* ; Anemia, Aplastic* ; Child* ; HLA-A2 Antigen ; HLA-DR2 Antigen ; Hospitals, University ; Humans ; Immunosuppression ; Immunosuppressive Agents ; Retrospective Studies

Kleine-Levin syndrome (KLS) is characterized by recurring episodes of hypersomnia, megaphagia, and abnormal behavior. We report two cases of KLS. Two boys, aged 18 (case 1) and 17 (case 2), had recurrent episodes of hyper-somnolence with compulsive eating or drinking and hypersexuality for several years. HLA-DR typing was HLA-DR3 and 13 in case 1 and HLA-DR4 and 10 in case 2. Case 1 showed hypersomnia with early onset of REM sleep on MSLT and frequent frontal intermittent rhythmic delta activity on EEG. Both cases showed no abnormalities on brain MRI. HLA-DR typing facilitates differentiation between KLS and narcolepsy by the absence of HLA-DR2.
Brain ; Disorders of Excessive Somnolence ; Drinking ; Eating ; Electroencephalography ; HLA-DR Antigens ; HLA-DR2 Antigen ; HLA-DR3 Antigen ; HLA-DR4 Antigen ; Kleine-Levin Syndrome* ; Magnetic Resonance Imaging ; Narcolepsy ; Sleep, REM

BACKGROUND: Genetic susceptibility to a variety of disease has been shown and it has recently been suggested that aplastic anemia is more common in adults who are HLA-DR2+ than in the general population. METHODS: To investigate whether certain HLA-DR gene is more common in children with aplastic anemia and HLA-DR2+ gene is associated with susceptibility to cyclosporine A (CyA), we analyzed the results of HLA-DR typing in 37 children with aplastic anemia with sequence specific oligonucleotide probe (SSOP) method. RESULTS: Eight patients were DR2+, and there was no more common than the normal population. All of the 8 patients with DR2+ were DRB1*1501+ with high resolution HLA typing. Of the 8 patients with DRB1*1501+, 3 patients were treated with CyA alone (2 patients) or CyA plus ATG (1 patient), 2 patients were treated with ATG (1 patient) or ALG alone (1 patient). Patients treated with CyA only or CyA plus ATG had either a complete (1 patient) or partial (2 patients) response and patients treated ATG or ALG alone had no response. CONCLUSION: Although incidence of HLA-DR2 was not significantly higher in children with aplastic anemia then normal population, response rate to CyA was significantly high in the DR2+ patients.
Adult ; Alleles* ; Anemia, Aplastic* ; Child* ; Cyclosporine ; Genetic Predisposition to Disease ; Histocompatibility Testing ; HLA-DR Antigens* ; HLA-DR2 Antigen ; Humans ; Incidence

OBJECTIVE: This study was conducted to elucidate the associations of HLA with systemic sclerosis (SSc) in Koreans. METHODS: HLA associations with SSc according to SSc-specific autoantibody status and clinical subsets (diffuse and limited) were investigated. HLA-A, B, and C antigens were typed by the serological method using microlymphocytotoxicity test, and HLA-DR by DNA typing method using PCR-reverse hybridization and PCR-SSCP in 56 Korean patients with SSc and 226 healthy controls. For SSc patients, anti-Scl-70 and anicentromere antibodies were tested by double immunodiffusion and indirect immunofluorescence, respectively. RESULTS: The results of HLA class I antigen typing showed that the frequencies of HLA-A24, B52 and B62 were increased, whereas those of A33, B44 and B58 were decreased in SSc patients compared to healthy controls. The frequency of HLA-DR2 was significantly increased, whereas that of HLA-DR13 was decreased in patients with SSc compared to controls. Among HLA-DR2 alleles, both HLA-DRB1*1501 and *1502 were increased in SSc patients compared to controls. According to clinical status, HLA-DRB1*1501 was increased in limited SSc patients and that of DRB1*1502 was increased both in diffuse and limited SSc patients compared to controls. According to autoantibody status, HLA- DRB1 1502 was significantly increased in anti-Scl-70-positive SSc patients and that of DRB1 1501 was increased in anti-Scl-70-negative SSc patients compared to controls. The association of HLA-DR2 alleles with SSc according to clinical subsets and anti-Scl-70 antibody status revealed that the frequency of HLA- DRB1 *1501 was significantly increased in anti-Scl-70-negative limited SSc patients compared to controls. CONCLUSIONS: These results suggest that different HLA-DR2 alleles are associated with different types of SSc in Koreans. HLA-DRB1 1502 shows strong association with anti-Scl-70-positive SSc, and DRB1 1501 with anti-Scl-70-negative limited SSc. It is concluded that the pathogenesis of SSc in Koreans is in part, based on the same genetic background.
Alleles ; Antibodies ; Asian Continental Ancestry Group ; DNA Fingerprinting ; Fluorescent Antibody Technique, Indirect ; HLA-A Antigens ; HLA-A24 Antigen ; HLA-DR Antigens ; HLA-DR2 Antigen ; HLA-DRB1 Chains ; Humans ; Immunodiffusion ; Scleroderma, Systemic*

The authors reported a case and its diagnostic process of post-traumatic narcolepsy which had developed after a head trauma. The 51-years-old patient showed frequent generalized paralytic attack, which was aggravated during stressful situation, diet time, and in front of hospital staffs. During the paralytic attack, consciousness was alert, and he never collapsed to hurt. All laboratory findings including serum potassium level were within normal limit, and also brain imaging studies and electroencephalography revealed no specific abnormal findings. Our clinical impression was a conversion disorder or a malingering at first, but after the detailed history taking and the careful observation, daytime sleep attack and some sleep problems were revealed. Thus nocturnal polysomnography and multiple sleep latency test(MSLT) were performed, and then the authors could diagnose as "narcolepsy". HLA-DR2 typing was negative. After imipramine trial, the frequency and the intensity of attack was dramatically reduced. The authors concluded that narcolepsy should be considered in the differential diagnosis of sleepiness or transient loss of muscle tone after traumatic brain injury.
Brain Injuries* ; Cataplexy ; Consciousness ; Conversion Disorder ; Craniocerebral Trauma ; Diagnosis, Differential ; Diet ; Electroencephalography ; HLA-DR2 Antigen ; Humans ; Imipramine ; Malingering ; Narcolepsy* ; Neuroimaging ; Polysomnography ; Potassium

BACKGROUND: Hepatitis B virus (HBV)-associated glomerulonephritis (HBGN) occurs with high prevalence in Asia, and accounts for over 30% of secondary glomerulonephritis in Korea. However, the association between HLA and HBGN has been hardly reported upon in the literature. METHODS: A total of 50 Korean patients with HBGN, 100 HBsAg (-) healthy controls and 89 HBsAg (+) controls (subjects with chronic HBV infection, HBsAg positive at least for 6 months) were included. HLA-DR typing was done using a reverse sequence specific oligonucleotide typing kit and HLA-DRB1 genotyping was done for HLA-DR2 positive samples by PCR-single strand conformational polymorphism method. RESULTS: In the HBGN patients, HLA-DR2 was highly significantly increased compared with HBsAg (-) controls (p=0.0002, corrected p=0.002, OR=4.0) and also compared with HBsAg (+) controls (p= 0.0005, corrected p=0.006, OR=3.7). Different HLA- DR2 alleles were strongly associated with different pathologic subtypes of HBGN: DRB1*1502 was associated with membranoproliferative glomerulonephritis (MPGN) (p=0.0003, corrected p=0.004, OR=14.5), and DRB1*1501 with membranous nephropathy (MN) (p= 0.05, OR=3.8). These associations were also found to be significant compared with HBsAg (+) controls (HBV-MPGN, p=0.002; HBV-MN, p=0.04). DR13 was found to have some protective effect in HBV infection (p=0.01, OR=0.3) and DR11 was found to be weakly associated with HBV infection (p=0.01, OR= 4.6), however these HLA alleles were not associated with disease susceptibility to HBGN. CONCLUSION: These results suggest that HLA- DR2 or a closely associated genetic factor is associated with disease susceptibility to HBGN, and different HLA-DR2 subtypes are associated with different pathologic subtypes of HBGN in Koreans.
Alleles ; Asia ; Disease Susceptibility ; Fibrinogen ; Glomerulonephritis* ; Glomerulonephritis, Membranoproliferative ; Glomerulonephritis, Membranous ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; HLA-DR Antigens* ; HLA-DR2 Antigen ; HLA-DRB1 Chains ; Humans ; Korea ; Prevalence