• 대한두경부종양학회지
• /
• 제13권1호
• /
• pp.16-23
• /
• 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.

• 대한미생물학회지
• /
• 제21권2호
• /
• pp.171-179
• /
• 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.

• 대한수혈학회지
• /
• 제29권3호
• /
• pp.310-319
• /
• 2018

배경: 최근 차세대염기서열분석법(Next Generation Sequencing: NGS)을 이용한 HLA 형별 분석에 대한 연구가 활발히 진행되고 있다. 이에 HLA 고해상도 분석법의 내재적 한계인 위상 모호성의 문제를 해결하고, 대량 검체 처리가 가능한 NGS 기반 고해상도 HLA 형별 검사법을, 자체 기술로 개발하고자 본 연구를 실시하였다. 방법: HLA NGS를 위한 핵산 추출 조건, 라이브러리 제작 및 PCR 체계 확립, 그리고 생물정보학을 이용한 HLA 형별 분석법을 개발하였다. 본 기관에서 개발한 NGS 기반 HLA 형별 검사의 정확성을 알아보기 위해 SSOP법으로 HLA 형별을 알고 있는 192개 검체와 SBT법으로 HLA 형별을 알고 있는 28개 검체에 대해 NGS 기반으로 검사한 HLA-A, -B 그리고 -DR 형별 결과를 비교해 보았다. 결과: 두 단계의 PCR을 통한 DNA 라이브러리 제작과 MiSeq (Illumina Inc., San Diego, USA) 기기를 이용한 NGS 시퀸싱 그리고 데이터 분석 시스템을 구축하였다. 기존에 HLA 형별을 알고 있는 220개 혈액 검체에 대해 NGS 기반 HLA 형별검사 결과가 모두 일치함을 확인하였다. 결론: NSG 기반 HLA 형별 검사법은 많은 검체를 효율적인 시간 내에 처리가 가능하여 조혈모세포기증 희망자 HLA 검사 등에 유용할 것으로 기대된다.

• BMB Reports
• /
• 제31권2호
• /
• pp.111-116
• /
• 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.

• 생물정신의학
• /
• 제1권1호
• /
• pp.79-87
• /
• 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.

• Journal of Periodontal and Implant Science
• /
• 제17권1호
• /
• pp.104.2-104.2
• /
• 1987

• 사상체질의학회지
• /
• 제14권1호
• /
• pp.90-99
• /
• 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.

• 대한임상검사과학회지
• /
• 제55권3호
• /
• pp.132-142
• /
• 2023

서울대학교병원 진단면역검사실에서 HLA 형별 검사를 위한 결과 산출하는 과정에서 HLA-DR 검사 시행 건수 총 611건 중 Lot No.20의 시약에서 빈번히 나타나는 위양성과 위음성으로 의심되는 특이 bead 들의 반응을 발견하게 되었다. 따라서 정확한 결과 산출과정을 모색하기 위하여 특이 bead들의 cut-off 수정을 하지 않은 검사결과 533건과 특이 bead의 cut-off 수정을 한 뒤 결과 산출을 한 78건의 사례들을 가지고 cut-off 수정을 야기시키는 요인을 여러 변수로서 규명하고자 하였다. 검체대상의 인구통계특성과 cut-off 수정 여부를 확인하기 위해 빈도분석, 검사실의 습도를 변수로 넣어 기술통계를 진행하였고, cut-off 수정 여부와 인구통계특성의 연관성을 확인하기 위하여 교차분석을 시행, cut-off 수정 여부에 따른 습도의 차이를 검증하기 위해 독립표본 t검증을 실시하였다. 마지막으로 습도수준에 따른 cut-off 수정비율의 관계를 검증하기 위해 로지스틱 회귀분석을 실시하였다. 결과적으로 검사실의 습도 수준이 증가함에 따라 cut-off 수정사례는 0.986배 감소하는 것으로 나타났다. 이는 습도가 낮아질수록 cut-off 수정률이 증가한다는 것을 의미한다. 따라서 검사실의 습도 또한 HLA typing 결과에 영향을 미치는 요인임을 시사한다.

• 생명과학회지
• /
• 제18권9호
• /
• pp.1202-1206
• /
• 2008

본 연구에서 정상적인 baboon의 흉선조직 및 폐조직에서 HLA-DR과 PGP9.5항원에 대한 반응성을 나타내는 수지상세포 형태의 세포가 축적되는 것을 보았다. 하지만, 이런 세포들은 baboon 이 BPD즉 폐이형성증에 걸리게 되면 사라진다는 것을 확인하였다. 그리고 140일 제태기간보다 125일 제태 기간을 보낸 미성숙 baboon이 HLA-DR을 가지는 세포가 더 많아 진다는 것을 관찰할 수 있었고 이로 인해 BPD동물모델을 구축하는데 125일 제태 기간을 보낸 동물이 훨씬 적합하다는 것을 알았다. 또한 bombesin의 항체인 2A11을 처리한 baboon (125d-14d/PRN)의 폐조직에서는 정상수준의 HLA-DR positive세포들이 관찰되었다. 더욱이, Baboon의 흉선으로부터 분리한 thymocyte로 bombesin에 대한 chemotaxis를 수행한 결과 세포이동 반응성을 보였다. 이러한 결과들은 생체 내 BLP들을 차단하면 BPD에 의해 야기된 폐이형성증을 막을 수 있고 2A11항체가 수동 면역제로 폐이형성증을 치료할 수 있는 치료제로써의 가능성을 제시하는 것이다.

• BMB Reports
• /
• 제32권6호
• /
• pp.529-534
• /
• 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.