• 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 Chest Surgery
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• v.43 no.5
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• pp.499-505
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• 2010

Background: There have been several reports using animal experiments that CD1-restricted T-cells have a key role in tumor immunity. To address this issue, we studied the expression of markers for CD1c+ myeloid dendritic cells (DCs) isolated from peripheral blood in the clinical setting. Material and Method: A total of 24 patients with radiologically suspected or histologically confirmed lung cancer who underwent pulmonary resection were enrolled in this study. The patients were divided according to histology findings into three groups: primary adenocarcinoma of lung (PACL), primary squamous cell carcinoma of lung (PSqCL) and benign lung disease (BLD). We obtained 20 mL of peripheral venous blood from patients using heparin-coated syringes. Using flow-cytometry after labeling with monoclonal antibodies, data acquisition and analysis were done. Result: The ratio of CD1c+CD19- dendritic cells to CD1c+ dendritic cells were not significantly different between the three groups. CD40 (p=0.171), CD86 (p=0.037) and HLA-DR (p=0.036) were less expressed in the PACL than the BLD group. Expression of CD40 (p=0.319), CD86 (p=0.036) and HLA-DR (p=0.085) were less expressed in the PACL than the PSqCL group, but the differences were only significant for CD86. Expression of co-stimulatory markers was not different between the PSqCL and BLD groups. Expression of markers for activated DCs were dramatically lower in the PACL group than in groups with other histology (CD40 (p=0.005), CD86 (p=0.013) HLA-DR (p=0.004). Conclusion: These results suggest the possibility that CD1c+ myeloid DCs participate in control of the tumor immunity system and that low expression of markers results in lack of an immune response triggered by dendritic cells in adenocarcinoma of the lung.

• The Journal of the Korean Society for Microbiology
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• v.21 no.2
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• pp.233-241
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• 1986

Patients of chronic hepatic diseases(n=107) including chronic hepatitis caused by hepatitis B virus infections(n=31), liver cirrhosis(n=53), and hepatocellular carcinoma(n=23) were examined to ascertain genetic relationship between chronic hepatic diseases and histocompatibility antigen. Peripheral blood lymphocytes were separated from whole blood by the method of Ficoll/Hypaque gradient. Total 54 histocompatibility antigens(class I antigens: 41, class II antigens: 13) were analysed by performing of complement dependent microlymphocytotoxicity method using Terasaki's and Catholic Medical College tissue typing plates. HLA antigen frequencies were compared with those of 661 normal controls. The following results were obtained: 1. HLA antigen frequencies of HLA-Bw46, -Bw76, -Cw1, -Cw6, and HLA-DR8 in chronic hepatitis patients were shown to be higher than those in controls(P<0.01). 2. HLA antigen frequencies of HLA-Bw46, -Cw7(P<0.01), and HLA-B37, -Bw58, -Cw1, -MT1(P < 0.05) in liver cirrhosis patients were shown relatively higher frequencies than those in controls. 3. In patients with hepatocellular carcinoma, antigens of HLA-A1, -A26, -Cw3, -Cw7 and HLA-DR6 were dominantly detected. 4. There were negative associations with HLA-Cw4, and -DR4 in patients of chronic hepatic diseases(P < 0.05).

• 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.

• 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.

• 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.

• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.16-17
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• 2002

The major histocompatibility complex (MHC) is an important susceptibility locus for many human autoimmune diseases. The structural and functional properties of HLA-DR molecules that are associated with susceptibility to several autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, have been defined.(omitted)

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.16-27
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• 2004

In the traditional Chinese medicine, Drynariae Rhizoma (DR) has been reported as a good enhancer for bone healing. DR, a plant widely used in the traditional medicinal systems of Korea, has been reported to possess antiviral, antibacterial and anti-inflammatory activities. Modulation of immune response to alleviate disease has been of interest for a long time. Plant extracts have been widely investigated for possible immunomodulatory properties. Thus, I have evaluated the anticellular and immunomodulatory properties of ethanolic extract of DR. DR extract inhibited proliferation of mitogen (phytohaemagglutinin; PHA) and antigen (purified protein derivative; PPD)-stimulated human peripheral blood mononuclear cells (PBMCs). In addition, DR inhibited growth of several cell lines of mouse and human origin. It also inhibited production of nitric oxide (NO), interleukin-2 (IL-2) and tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$. Intracytoplasmic $interferon-{\gamma}\;(IFN-{\gamma})$ and expression of cell surface markers, CD16 and HLA-DR, on human PBMC, were not affected on treatment with DR but CD25 expression was down regulated. This study demonstrates the antiproliferative and immunosuppressive potential of ethanolic extract of DR in vitro.

• Sleep Medicine and Psychophysiology
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• v.8 no.2
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• pp.107-112
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• 2001

Introduction: Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and cataplexy, is known to be closely associated with the human leukocyte antigen (HLA) DQB1*0602. Several studies have suggested that HLA-DQB1*0602 is strongly linked with narcolepsy-cataplexy. However, no studies have yet been made on whether HLA DQB1*0602 is associated with Korean patients with narcolepsy. This study was designed to investigate the frequency of HLA-DQB1*0602 of Korean patients with narcolepsy. Methods: Twenty patients were selected (mean age: $28.2{\pm}3.0$, 11 men and 9 women). The patients were confirmed to have narcolepsy by the overnight polysomnography and multiple sleep latency test (MSLT) in addition to their clinical history and symptoms at St. Vincent's Hospital and Korea University Hospital Sleep Disorders Clinic. Any subjects co-morbid with other hypersomnic sleep disorders such as sleep apnea or periodic limb movements during sleep were excluded. Clinical data was collected through a semi-structured interview for narcoleptic patients. All patients and 21 control did HLA typing for the presence of DQB1*0602. Results Obtained were as Follows: 1) Mean sleep latency was 2.4 (${\pm}2.0$ minutes) and mean frequency of sleep-onset REM period was 3.0 (${\pm}1.6$) by MSLT. 2) Characteristic symptoms of narcolepsy investigated were as follows: excessive daytime sleepiness (100%), cataplexy (100%), sleep paralysis (60%), hypnagogic hallucination (70%) and disrupted nocturnal sleep (75%). 3) Strong emotional expression such as laughing (80%) and joking (70%) triggered cataplexy which affects the knee and leg region (80%) and jaw region (30%). 4) HLA-DR2 was found in 90% of patients and 35% in controls. The frequency of HLA-DQB1*0602 in patients and controls was 90%, and 24%, respectively. Conclusions: These results, which exhibit high HLA-DQB1*0602 expression in Korean patients with narcolepsy, suggest that HLADQB1*0602 could be a strong genetic marker in narcolepsy.

• Journal of Veterinary Clinics
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• v.28 no.4
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• pp.399-402
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• 2011

In recent years, the mesenchymal stem cells (MSC) derived from various tissues have been widely tested for developing cell therapies, tissue repair and transplantation. Although there has been much interest in the immunomodulatory properties of MSC and their immunologic reactions following autologous, allogeneic and xenogenic transplantation of MSC in vivo, up to date, the expression of immunogenic markers, such as class I and II human leukocyte antigens (HLA), after differentiation of human umbilical cord blood (hUCB)-derived MSC has been poorly investigated and require extensive in vitro and in vivo testing. In this experiment, the expression of the HLA-ABC and HLA-DR on hUCB-derived MSC have been tested by immunocytochemical staining. The undifferentiated MSC were moderately stained for HLA-ABC but very weakly for HLA-DR. In order to investigate the inhibitory effect of allogeneic lymphocytes on proliferation of MSC, the MSC were cultured in the presence or absence of peripheral allogeneic lymphocytes stimulated with concanavalin A. The allogeneic lymphocytes did not significantly inhibit MSC proliferation. We conclude that hUCB-MSC expressed moderately class I HLA antigen while almost negatively class II HLA antigen. The MSC have an immunomodulatory effect which can suppress the allogeneic response of lymphocytes. These in vitro data suggest that allogeneic MSC derived from cord blood can be useful candidate for allogeneic cell therapy and transplantation without a major risk of rejection.