• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.624-633
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• 2005

Purpose : This study analyzed the expression of HLA-DR and DQ genotypes and anti-thyroid autoantibodies[anti-thyroid peroxidase(TPO) and anti-thyroglobulin(TG) antibodies] in Korean patients with type 1 diabetes(T1DM) to investigate the susceptible HLA alleles to T1DM in Korea and the prevalence of thyroid autoantibodies and their significance for the development of thyroid disorders. Methods : A total of 59 Korean patients with type 1 diabetes[26 males, median age 13.7 years(range 5.7-29.9 years), diabetes duration 7.6 years(-1.7-22.5 years)] were enrolled in this study, and 200 healthy Koreans without a family history of diabetes were selected as a normal control for the comparison of HLA genotypes. Seventeen patients with anti-TPO or anti-TG were followed [median duration 3.96 years(1 day-10.7 years)] with measurement of anti-TPO, anti-TG, $T_3$, $T_4$ or free $T_4$, TSH levels and physical examinations. HLA-DR and DQ genotyping were done by PCR-SSO, PCR-SSCP, PCR-RFLP and PCR-SSP methods. Results : HLA analysis showed higher frequencies of HLA-DRB1*0301, *090102 and DQB1*0201, *030302 alleles, DRB1*0301/*090102, *090102/*090102 and DQB1 *0201/*030302, *030302/*030302, *0201/ *0302 genotypes in T1DM patients compared to controls(Pc<0.05). Fifteen(25.4 percent) had anti-TPO antibody, 12(20.3 percent) had anti-TG, 17(28.8 percent) had either autoantibody and 10(16.9 percent) had both autoantibodies. No clinical or subclinical hypothyroidism developed during follow-up after the first detection of anti-thyroid autoantibody. There was no significant correlation between thyroid autoimmunity and gender, onset age of T1DM, and diabetes duration, respectively(P>0.05). Conclusion : We thought this unique HLA-DR, DQ allele distribution might be an important factor for the low incidence of T1DM in Korea. And a high prevalence of thyroid autoantibodies in these populations suggests examinations of thyroid antibodies should be performed regularly. Optimal age for the initial screening and the frequency of re-screening for associated thyroid autoimmune diseases in T1DM remains to be determined through prospective follow-up.

• Journal of Korean Neurosurgical Society
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• v.46 no.6
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• pp.558-563
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• 2009

Objective : Moyamoya disease (MMD) is an uncommon cerebrovascular disorder, characterized by progressive occlusion at the terminal portion of the internal carotid artery. Incidence of the disease is high in East Asia and familial MMD accounts for about 15% of the disease. Although the pathogenesis is unknown, association of HLA class I or II alleles with MMD has been reported with conflicting results. We investigated whether there is a difference in HLA class II association between familial and non-familial forms of the disease. Methods : A total of 70 Korean children with MMD, including 16 familial cases (10 probands), and 207 healthy controls were studied. Among familial cases, only 10 probands were used for the HLA frequency analysis. High resolution HLA-DRB1 and DQB1 genotyping was performed using polymerase chain reaction (PCR)-sequence specific oligonucleotide hybridization and PCR-single strand conformation polymorphism methods. Results : The phenotype frequencies of HLA-DRB1*1302 (70.0%) and DQB1*0609 (40.0%) were significantly increased in familial MMD compared to both controls [vs. 15.5%, corrected p ($p_c$) = 0.008, odds ratio (OR) = 12.76; vs. 4.3%, $p_c\;=\;0.02$, OR = 14.67] and non-familial MMD patients (vs. 14.8%, $p_c\;=\;0.02$, OR = 13.42; vs. 1.9%, $p_c\;=\;0.02$, OR = 35.33). The frequencies of DRB1 and DQB1 alleles in non-familial MMD patients were not significantly different from those in controls. Conclusion : Our findings suggest that the genetic polymorphism of HLA class II genes or other closely linked disease relevant gene(s) could be a genetic predisposing factor for familial MMD.

• Biophysical Society Newsletter
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• v.7 no.2
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• pp.6-9
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• 2001

• IMMUNE NETWORK
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• v.23 no.2
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• pp.17.1-17.16
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• 2023

Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8⁺ and CD4⁺ T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8⁺ T cell responses were significantly higher than CD4⁺ T cell responses. CD8⁺ T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4⁺ T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×105 CD8⁺ or CD4⁺ T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.

• Sleep Medicine and Psychophysiology
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• v.7 no.2
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• pp.115-119
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• 2000

Objectives Summary: A 20-year-old man was presented with a history of difficult waking for 10 years. He suffered from morning headache, chronic fatigue and mild daytime sleepiness but had no history of irresistible sleep attack, cataplexy, hypnagogic hallucination or sleep paralysis. Methods: Night polysomnography (PSG), multiple sleep latency test (MSLT) and HLA-typing were carried out. Results: The PSG showed short sleep latency (4.0 min) and REM latency (2.5 min), increased arousal index (15.7/hour), periodic limb movements during sleep (PLMS index=8.1/hr) with movement arousal index 2.1/hr and normal sleep efficiency (97.5%). The MSLT revealed normal sleep latency (15 min 21 sec) and 4 times sleep-onset REM (SOREM). HLA-typing showed DQ6- positive, that corresponded at the genomic level to the subregion DQB1*0601, which was different from the usual locus in narcolepsy patients (DQB1*0602 and DQA1*0102). Conclusion: Differential diagnosis should be made with circadian rhythm disorder and other causes of primary waking disorder. The possibility of a variant type of narcolepsy could be suggested with an unusual clinical manifestation and a new genetic marker.

• Childhood Kidney Diseases
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• v.4 no.1
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• pp.33-39
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• 2000

Purpose: Our study was designed to investigate the association of MHC Class II (DR, DQ) allele with IgA nephropathy and its significance as a prognostic factor for progression to ESRD Material and Methods: 69 children with IgA nephropathy with normal renal function(serum creatinine $\leq$ 1.5mg/dL) was classified as group A and 70 patients who received renal transplantation due to IgA nephropathy were selected as group B. The HLA-DQB1 and HLA-DRB1 alleles were studied by polymerase chain reaction using sequence specific primers. We have compared the difference in alleles between these two groups and with normal control and also examined any possible effect of the MHC class II genes on the histopathological severity and prognosis of IgAN. Results: Mean age was $8.8{\pm}2.9$ years in group A and $35.0{\pm}15.5$ years in group B. Male to female ratio was 2.8:1 in group A and 2.5:1 in group B. There was a significantly higher frequency of HLA-$DQB1^*03\;and\;DQB1^*05$ in Group B. The frequency of HLA-$DQB1^*0302\;and\;^*05031$ allele had increasing tendency in Group B(P<0.05). HLA-$DRB1^*03\;and\;^*05$ were more common in Group B(P<0.05). HLA-$DRB1^*04$ allele was the most common DR alleles in both group, but there was no statistical significance. There were no significant correlation with MHC class 13 genes on the hjstopathological severity in Group A. Conclusion: In conclusion, $HLA-DQB1^*0302\;and\;HLA-DQB1^*05031 $ allele seemed to be more common in transplanted patients compared to group with normal renal function suggesting that this allele is associated with poor prognosis in IgAN. However larger studies and follow up are required to confirm this due to uncharacterized heterogeneity in etiopathogenesis of IgA nephropathy and possibly one or more than one gene may exert influence in determining susceptibility to the diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4125-4128
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• 2014

The median ages at death from cancers between 1985 and 2005 were calculated to demonstrate that inherent anticancer mechanisms may be a common pathway for different cancers. Seventy-eight patients with gastric, liver and lung cancers, were recruited in the solid cancer group. The leukemia group consisted of 31 patients with three main types of leukemia. The controls were 100 healthy individuals. The samples were typed using an HLA-DR/DQ PCR-SSP typing kit. The results showed that the median ages at death from all causes were 64.7 years in 1985 and 70.1 years in 2005. The range of the median ages at death from all cancers was similar to the corresponding value for deaths attributed to all causes. The frequency of $DRB1^*03$ was 9.6% in the solid cancer group and 3.0% in the control group (p<0.05). The frequency of $DRB1^*04$ in the leukemia group were significantly lower than that of the control (p<0.05). $DRB1^*13$ and $DRB1^*06$ frequencies in the leukemia group were significantly higher than those of the controls (p<0.05). It is suggested that inherent anti-cancer mechanisms may be a common pathway for different cancers and are associated with the immune system and HLA.

• Clinical and Experimental Pediatrics
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• v.46 no.5
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• pp.467-473
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• 2003

Purpose : The Epstein-Barr virus(EBV), gamma herpesvirus, is an important pathogen that is widespread around the world. The EBV causes various diseases depending on the geographic location, and on the immunity or the premorbid condition of the person exposed to EBV. To evaluate EBV typing may be the most important step to figure out the pathogenesis of EBV associated diseases, and we need to re-evaluate the pathologic role of human leukocyte antigen(HLA) in developing Epstein- Barr virus associated acute infectious mononucleosis by using newly developed methods. Methods : This study included 24 children(age range : 6 to 13 years), serologically confirmed with acute infectious mononucleosis. The control group for the HLA type consisted of 200 age-matched healthy children. To classify HLA I, modified ARMs-PCR was used, while modified PCR-SSOP was utilized in typing of HLA II. Also, we performed EBV typing in study patients by using a one-step PCR. Results : The results of HLA types : In HLA class I, HLA-A24 was positive in 69 of 200 healthy children and positive in 14 of 24 patients in the study group(relative risk : 3.5724, chi-square; 5.26, P<0.05). In HLA class II, HLA-DRB1*07 was detected in 18 of 200 healthy children, and eight of 24 patients in the study group(relative risk; 506173, chi-square; 9.73, P<0.01). The results of EBV types : In the research group, 20(83.8%) of 24 patients were shedding type A virus, while 4(16.7%) were type B. Conclusion : We conclude that development of infectious mononucleosis may be associated with HLA types, and these results suggest that acute infectious mononucleosis could have hereditary traits. And we confirm that type A EBV is highly prevalent in patients with acute infectious mononucleosis in Korea. Also, our results suggest that further large scale studies, including adult groups, regarding the association between pathogenesis of EBV with HLA-DP or HLA-DQ will be warranted.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.367-377
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• 2003

Background : It is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). Methods : HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. Results : Among the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was significantly increased in PTB patients (4.0% vs. 14.9%, p=0.004), showing similar increases in both DS and MDR cases. There was also an association of HLA alleles with the clinical severity of the disease according to the extent of lung lesion. Significantly increased frequencies of DRB1*08032 (4.2% vs. 32.6%, p=0.007) and DQB1*0601 (12.5% vs. 34.9%, p=0.047) were observed in more advanced (moderately & far advanced/DS and far advanced/MDR), compared with less advanced (minimal/DS and moderately advanced/MDR) lung lesions. Although DRB1*0701, DQB1*0202 and DQB1*0609 showed significant increases in different subsets of the disease, these HLA alleles did not show consistent association with disease severity. Conclusion : HLA-DRB1*08032 and DQB1*0601 alleles were associated with genetic susceptibility to MDR-TB in Korean patients, and also with disease severity and progression of PTB.