• Title/Summary/Keyword: HLA-DR

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Thyrocyte HLA-DR Expression in Variety of Thyroid Diseases (갑상선 질환들에서 여포세포의 HLA-DR발현)

  • Chang Eun-Sook;Sohn Soo-Sang;Cho Seung-Che;Kim In-Ho;Kim Sang-Pyo;Kang Joong-Shin
    • Korean Journal of Head & Neck Oncology
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    • v.13 no.1
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    • pp.16-23
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    • 1997
  • Although normal thyroid epithelial cells do not constitutively express HLA-DR antigen, their expression in wide spread within thyroid glands obtained from the human with autoimmune thyroid disease and with many neoplastic thyroids. We have, therefore, studied immunohistochemically with regard to the expression of HLA-DR antigen of thyroidectomy specimens from 50 patients of various thyroid diseases with use of paraffin-embedded tissue. One or two sections from each case were stained with commercially available mouse monoclonal antibody for class II HLA-DR antigen(HLA-DR/Alpha, DAKO) and examined by semiquantitative counting system for thyrocytes, neoplastic thyrocytes and other cells expressing HLA-DR antigen. All patients with lymphocytic thyroiditis(2/2) and diffuse hyperplasia(Graves' disease)(5/5), most patients with Hashimoto's disease(9/ll) expressed HLA-DR antigens in thyrocyte with abundant HLA-DR expressing lymphocytic infiltrates with lymph follicle formation in its vicinity or adjacent to the lesion. Most patients with papillary carcinoma(9/1l) had HLA-DR antigen detected in malignant thyrocytes ; while follicular carcinoma(0/3) and follicular adenoma(0/5) did not have detactable HLA-DR immunoreactivity. Adenomatous goiter(3/7) had HLA-DR antigen detected focally in lesser than half cases. Conversely, in four papillary carcinomas and three adenomatous goiters, HLA-DR expression of thyrocytes was found in the absence of HLA-DR expressing lymphoid infiltrates. In such cases therefore other factors more than thyroid autoimmunity must be causative for HLA-DR immunoreactivity. The results of this study indicate as follows. 1) The expression of HLA-DR on thyrocytes involved in autoimmune reactions appeared to be secondary to cytokine release from associated lymphocytic infiltrates. 2) Thyrocytes in thyroid lesions with equal degrees of lymphocytic infiltration without HLA­DR expression exhibited no HLA-DR immunoreactivity. 3) In neoplastic thyrocytes, most papillary carcinoma(9/11) exhibited detactable HLA-DR expression, while follicular carcinoma/adenoma(0/3/0/5) exhibited no detactable HLA-DR immunoreactivity which suggest the existence of divergent mechanisms inducing and modulating HLA-DR expression of different types of neoplastic thyrocytes.

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HLA Class II Variants and Disease Associations (HLA 제 2 항원계 유전자 다형성(genomic polymorphism)과 질병감수성의 연관)

  • Kim, Se-Jong
    • The Journal of the Korean Society for Microbiology
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    • v.21 no.2
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    • pp.171-179
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    • 1986
  • The HLA class II region encodes a series of polymorphic glycoproteins that form cell surface heterodimers each consisting of one $\alpha$ and one $\beta$ chain. Thess class II molecules are encoded by genes clustered within three loci. DP, DQ, and DR are functfonally implicated as regulatory signals in intercellular communication during the immune resposes. The phenotypic hallmark of the HLA complex is a high degree of structural and functional polymorphism. Detailed analysis. of such polymorphisms should aid in understanding the molecular basis for associations between HLA and diseases. We have used techniques of restriction enzyme fragment analysis by Southern blotting to investigate polymorphisms associated with DQ $\beta$ class II genes on haplotypes expressing the HLA-DR4 and -DQw3 specificities. The endonucleases Hind III and Bam HI were used to identify a specific DQ $\beta$ genomic polymorphism that precisely corrresponds with the reactivity of a monoclonal antibody A-10-83, previously shown to define a serologic split of DQw3. This study identifies two allelic DQ va. riants. DQw3.1 and DQw3.2. We used these specific genotypic markers to investigate the genomic basis of the association of DR4 with insulin-dependent diabetes mellitus(IDDM) and seropositive juvenile rheumatoid arthritis(JRA). The DR4 positive IDDM demonstrate the predominant expression of DQw3.2 and the very rare expression of DQw3.l. However, in haplotype matched siblings from two IDDM families, all of the DR4 positive siblings display a IDDM-associated DQw3.2 allele. Thus, both affected and healthy individuals can carry the same haplotypes and genomic markers, demonstrating that thess specific allelic variants are genetic elements that indicate a increased risk of IDDM but are not in fact disease specific. We contrasted this result with a similar analysis of patients with another DR4-associated disease, JRA. In contrast to the preponderance of the DQw3.2 allele in IDDM, the JRA patients expressed either the DQw3.1 or the DQw3.2 allele and sometimes both, without apparent association with disease expession. The different genomic markers reported here within HLA-DQ region potentially an analysis of HLA-associated function and disease susceptibility.

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Development of HLA-A, -B and -DR Typing Method Using Next-Generation Sequencing (차세대염기서열분석법을 이용한 HLA-A, -B 그리고 -DR 형별 분석법 개발)

  • Seo, Dong Hee;Lee, Jeong Min;Park, Mi Ok;Lee, Hyun Ju;Moon, Seo Yoon;Oh, Mijin;Kim, So Young;Lee, Sang-Heon;Hyeong, Ki-Eun;Hu, Hae-Jin;Cho, Dae-Yeon
    • The Korean Journal of Blood Transfusion
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    • v.29 no.3
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    • pp.310-319
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    • 2018
  • Background: Research on next-generation sequencing (NGS)-based HLA typing is active. To resolve the phase ambiguity and long turn-around-time of conventional high resolution HLA typing, this study developed a NGS-based high resolution HLA typing method that can handle large-scale samples within an efficient testing time. Methods: For HLA NGS, the condition of nucleic acid extraction, library construction, PCR mechanism, and HLA typing with bioinformatics were developed. To confirm the accuracy of the NGS-based HLA typing method, the results of 192 samples HLA typed by SSOP and 28 samples typed by SBT compared to NGS-based HLA-A, -B and -DR typing. Results: DNA library construction through two-step PCR, NGS sequencing with MiSeq (Illumina Inc., San Diego, USA), and the data analysis platform were established. NGS-based HLA typing results were compatible with known HLA types from 220 blood samples. Conclusion: The NSG-based HLA typing method could handle large volume samples with high-throughput. Therefore, it would be useful for HLA typing of bone marrow donation volunteers.

Generation of Anti-HLA-DR4 Specific Antibodies by Immunization of the Recombinantly Expressed Allelic Subtype-Specific Region of the $HLA-DRB1^*0405$ Molecules

  • Park, Jung-Hyun;Cho, Eun-Wie;Lee, Yun-Jung;Chung, Jin;Hahm, Kyung-Soo;Kim, Kil-Lyong
    • BMB Reports
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    • v.31 no.2
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    • pp.111-116
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    • 1998
  • HLA-DR4 is the dominant allele of MHC class II genes in Koreans. In particular, the $DRB1^*0405$ subtype has been reported to be almost exclusively expressed in Far East Asians, and has also been observed to be strongly associated with rheumatoid arthritis in Koreans and the Japanese. Identification of this specific allele has been mainly performed by PCR-based methods, which is often time consuming, costly, and involves tedious procedures such as the isolation of genomic DNA, PCR, and gel electrophoresis. To develop a more convenient tool for screening vast amounts of samples as well as to generate reagents which might also be used in other applications, in this study, antibodies were produced against this specific HLA subtype. By PCR, an allelespecific region covering the ${\beta}1$ domain of $DRB1^*0405$ was amplified and recombinantly expressed in E.coli. Immunization of Lewis rats with the purified protein yielded an allele specific antiserum. Western blot analysis showed the selective detection of the HLA-DR ${\beta}-chain$. Using this antiserum, established cell lines and peripheral blood lymphocytes were analyzed on their HLA haplotype by fluorescence activated flow cytometry. These novel antibodies will provide a powerful tool in the detection and investigation of DR4 alleles.

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The Frequencies and Disease-Association of HLA Alleles in Bipolar Patients (양극성 장애환자에서 HLA 대립형의 빈도와 질병연관성)

  • Jun, Tae-Youn
    • Korean Journal of Biological Psychiatry
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    • v.1 no.1
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    • pp.79-87
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    • 1994
  • For the purpose of evaluating the human leukocyte antigen(HLA) disease-association with bipolar disorder, HLA class I and class II allelic frequencies were assessed in 37 bipolar patients and were compared to the data from normal population. HLA class 1 typing was performed with microlymphocytotoxicity method while class II(DRB1) genotyping with reverse dot blot hybridization and sandwich method. Statistical analysis consisted of relative risk, Haldane's modified relative risk, Fisher's exact test and Bonferoni's corrected P. The results were as follows : 1) Bipolar patients showed increased allelic frequency of HLA A3 which has statistical significance. 2) Allelic frequencies of HLA B7, B14 and B54 were higher, while those of B51 and B55 were lower in bipolar patients, but they were not statistically significant. 3) Both of increased frequencies of DR2 in bipolar patients and DR15 in normal controls had statistical significance. The results of the present study suggested that some of HLA allelic types might be associated with bipolar disorder. To clarify the genetic influence of HLA to bipolar disorder, we should do consecutive study of bipolar disorder with new information about HLA system including alleles.

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A study on the correlation between Sasang Constitution and HLA type (사상체질(四象體質)과 HLA type과의 상관성(相關性)에 관(關)한 연구(硏究))

  • Koh, Byung-Hee;Song, Il-Byung;Ha, Man-Su
    • Journal of Sasang Constitutional Medicine
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    • v.14 no.1
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    • pp.90-99
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    • 2002
  • Exact constitutional classification is especially important in Sasang Constitutional Medicine. Therefore, most studies on the Sasang Constitutional medicine have been focused on how accurately to classify Sasang Constitution. Recently, there have been reported on the studies about relationship between genetic polymorphism and Sansang Constitution. The purpose of this study is to investigate whether there is any correlation between Sasang Constitution and HLA type. Polymorphism of HLA genes have been known to be important role in transplantation, autoimmune disease, immune response against infection. This study was concentrated on a relationship of HLA-A, -C, -DR, and -DQ types with Sasang Constitution. Results are as following. 1. In the case of HLA-A, there was no significant difference. Only $HLA-A^*31$ has a tendency which Soyangin is less frequent than Soeumin and Taeumin. 2. In the case of HLA-C, there was significant difference between Sasang Constitution and HLA type. In persons having $HLA-C^*04$ allele, Taeumin is more frequent than Soyangin and Soeumin. On the other hand, Soyangin is more frequent than Taeumin and Soeumin in $HLA-C^*07$ allele. $HLA-C^*14$ has a tendency which Soeumin is more frequent than Soyangin and Taeumin. 3. In. the case of HLA-DR type and HLA-DQ type, there was no significant difference among Sansang Constitution. On the study of correlation between Sasang Constitution and HLA type, there was little statistical significance and tendency. This study was the first try about presentation of frequency on the HLA alleles corresponding with Sasang Constitution. I think that more study on the relationship between HLA gene and Sasang Constitution is necessary by method of large case research and various statistical analysis.

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Association between False Positive, False Negative, High-Background Cases and Humidity in One Lambda LABTypeTM HLA-DR Typing (One Lambda LABTypeTM을 이용한 HLA- DR Typing시 나타나는 위양성과 위음성, High-Background 사례와 검사실 습도의 관계분석)

  • Hyang Son AN;Minsung SOHN
    • Korean Journal of Clinical Laboratory Science
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    • v.55 no.3
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    • pp.132-142
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    • 2023
  • Human leukocyte antigen (HLA) typing was performed in the diagnostic immunology laboratory of the Seoul National University Hospital. Among 611 HLA-DR tests, specific bead reactions suspected of being false positive and false negative in Lot 20 reagents were found. Therefore, we aimed to identify the factors causing cut-off corrections by examining cases where cut-off corrections were not made for 533 test results and cases where cut-off corrections were made for 78 cases after the cut-off corrections of specific beads. Frequency analysis was conducted to verify the demographic characteristics, and descriptive statistics were used to assess the humidity in the laboratory as a variable. Cross-tabulation was done to examine the association between cut-off corrections and demographic characteristics. Independent samples t-tests were conducted to verify the difference in humidity based on cut-off corrections. Finally, logistic regression analysis was conducted to examine the relationship between humidity levels and the rate of cut-off corrections, and results showed as the humidity level in the laboratory highs, the number of cut-off corrections decreased by a factor of 0.986. This suggests cut-off corrections rate increases when the humidity lowers. Therefore, it indicates that humidity in the laboratory is also a factor that affects HLA typing results.

Dendritic-like Cells Accumulate in BPD Lung of Baboon (만성 폐질환인 폐이형성증을 보이는 baboon 폐조직에 Dendritic-like cell의 축적)

  • Lee, Jong-Hwan;Kim, Kwang-Hyeon
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1202-1206
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    • 2008
  • The present investigation demonstrates HLA-DR and PGP9.5 double positive cells accumulate thymus cortical region in normal baboon thymus and baboon lung. But, these cells disappeared in thymus and lung of bronchopulmonary dysplasia (BPD) animals. 125d GC animal model is more suitable for BPD than 140d GC animal. Anti-bombesin antibody, 2A11 treated baboon recover normal level of HLA-DR positive cells from BPD animal. In addition, thymocytes show responsiveness for bombesin. These observation suggest that blocking BLPs protects a chronic lung injury by BPD and 2A11 is possible agent for passive therapy of BPD.

Asymmetric Polymerase Chain Reaction-Single-Strand Conformation Polymorphism (Asymmetric PCR-SSCP) as a Simple Method for Allele Typing of HLA-DRB

  • Kang, Joo-Hyun;Kim, Kyeong-Hee;Maeng, Cheol-Young;Kim, Kil-Lyong
    • BMB Reports
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    • v.32 no.6
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    • pp.529-534
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    • 1999
  • Asymmetric PCR and single-strand conformation polymorphism (SSCP) methods were combined to analyze human leukocyte antigen (HLA)-DRB allele polymorphism. Asymmetric PCR amplification was applied to generate single-stranded DNA (ssDNA) using the nonradioactive oligonucleotide primers desinged for the polymorphic exon 2 region. The conformational differences of ssDNAs, depending on the allele type, were analyzed by nondenaturing polyacrylamide gel electrophoresis and visualized by ethidium bromide staining. The ssDNAs were clearly separated from double-stranded DNA without interference and obviously migrated depending on their allele type. This method was applied to the genomic DNA either from homozygous or from heterozygous cell lines containing the DR4 allele as template DNA using DR4-specific primers, and satisfying results were obtained. Compared to the standard PCR-SSCP method, this asymmetric PCR-SSCP method has advantages of increased speed, reproducibility, and convenience. Along with PCR-SSP or sequence-based typing, this method will be useful in routine typing of HLA-DRB allele.

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