• Title/Summary/Keyword: HLA-A

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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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A Study on HLA Federate Compliance Testing Process and its Applications (HLA 페더레이트 연동화 인증철차 및 적용사례)

  • 김용효;박헌근;이해관
    • Journal of the military operations research society of Korea
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    • v.30 no.1
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    • pp.81-91
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    • 2004
  • Since HLA (High Level Architecture) was selected as a standardized distributed simulation architecture by US DoD in order to guarantee interoperability among all types of simulations, weapons system and C4I systems, to improve reusability of developed models in mid 1990s, a large number of federates have been developed and certified in accordance with HLA specifications. This paper illustrates case studies on HLA compliance test which are helpful for developers and managers. Based on experiences obtained from international HLA compliance test of CJ21_NG being developed for ground warfare simulation during ROKA's BCTP and UFL exercises, compliance procedures of US Defense and Modelling Simulation Office (DMSO) are introduced, and detail information at each phase of compliance test is provided.

Distributions of HLA Microsatellite Markers and the Linkage Disequilibria between HLA and Microsatellites in Koreans (한국인에서 HLA 유전자 부위 내 Microsatellite 표지자의 분포와 HLA 대립유전자의 유전적 연관성)

  • Jang, Jung-Pil;Choi, Eun-Jeong;Yoon, Ho-Yeul;Choi, Hee-Baeg;Kim, Hee-Je;Cho, Byung-Sik;Min, Woo-Sung;Lee, Jong-Wook;Kim, Chun-Choo;Kim, Tai-Gyu
    • IMMUNE NETWORK
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    • v.7 no.3
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    • pp.149-157
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    • 2007
  • Background: The microsatellites within human leukocyte antigen (HLA) region show considerable polymorphism and strong linkage disequilibrium (LD) with HLA alleles. These microsatellites have been used for genetic analysis including disease mapping to understand susceptibility to autoimmune and infectious diseases. Also, use of microsatellites has recently been proposed as an approach for identifying non-HLA markers within the HLA region that could function as transplantation determinants and for the selection of potential donors for transplantation. Methods: To analyse the frequency of five microsatellites in the Korean population, genotyping for polymorphisms at five microsatellites markers (BAT2, MIB, DQCAR, D6S105 and TNFd) within HLA region was performed on 143 healthy Korean controls. Results: The most frequent genotype shown in healthy Korean controls were BAT2 8 (153 bp, 42.7%), MIB 1 (326 bp, 40.6%), DQCAR 3 (188 bp, 38.5%), D6S105 7 (126 bp, 58.0%) and TNFd 3 (128 bp, 58.0%). And common two-loci haplotypes were found as MIB 1-HLA-B*62 (HF: 10.6%), MIB 6-HLA-B*44 (HF: 7.8%), DQCAR 3-HLA-DRB1*13 (HF: 8.5%), TNFd 5-HLA-B*62 (HF: 7.8%) and D6S105 7-HLA-A*02 (HF: 16.2%). Conclusion: These data might provide useful information on the microsatellites markers with HLA region in Korean population and be helpful in further defining the clinical impact of these microsatellites.

14-bp Insertion/Deletion Polymorphism of the HLA-G gene in Breast Cancer among Women from North Western Iran

  • Haghi, Mehdi;Feizi, Mohammad Ali Hosseinpour;Sadeghizadeh, Majid;Lotfi, Abbas Sahebghadam
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.14
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    • pp.6155-6158
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    • 2015
  • Background: The human leukocyte antigen-G (HLA-G) gene is highly expressed in cancer pathologies and is one strategy used by tumor cells to escape immune surveillance. A 14-bp insertion/deletion (InDel) polymorphism of the HLA-G gene has been suggested to be associated with HLA-G mRNA stability and the expression of HLA-G. The aim of present study was to assess any genetic association between this polymorphism and breast cancer among Iranian-Azeri women. Materials and Methods: In this study 227 women affected with breast cancer, in addition to 255 age-sex and ethnically matched healthy individuals as the control group, participated. Genotyping was performed using polymerase chain reaction and electrophoresis assays. The data were compiled according to the genotype and allele frequencies, compared using the Chi-square test. Statistical significance was set at P<0.05. Results: In this case-control study, no significant difference was found between the case and control groups at allelic and genotype levels, although there is a slightly higher allele frequency of HLA-G 14bp deletion in breast cancer affected group. However,when the stage I subgroup was compared with stage II plus stage III subgroup of affected breast cancer, a significant difference was seen with the 14 bp deletion allele frequency. The stage II-III subgroup patients had higher frequency of deletion allele (57.4% vs 45.8%) than stage I cases (${\chi}^2=4.16$, p-value=0.041). Conclusions: Our data support a possible action of HLA-G 14bp InDel polymorphism as a potential genetic risk factor for progression of breast cancer. This finding highlights the necessity of future studies of this gene to establish the exact role of HLA-G in progression steps of breast cancer.

Design and Implementation of Interoperable Adaptor for Simulators Interoperation using IEEE 1516 HLA/RTI (IEEE 1516 HLA/RTI 기반 연동 시뮬레이션을 위한 연동 어댑터의 설계 및 구현)

  • Hong, Jeong-Hee;Sung, Chang-Ho;Ahn, Jung-Hyun;Kim, Tag-Gon
    • Journal of the Korea Institute of Military Science and Technology
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    • v.12 no.1
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    • pp.88-96
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    • 2009
  • Interoperation between heterogeneous simulators employs definition of standard protocols for data exchange and time synchronization among simulators. The High Level Architecture(HLA) is a specification of common services for such interoperation, which is approved as IEEE standard 1516. This paper presents the design and implementation of an interoperable adaptor which supports development of interoperable simulators under the IEEE 1516 HLA/RTI environment. The adaptor, KHLAAdaptor1516, is implemented as a library form which is linked to HLA-compliant simulators. Design of the adaptor employs a protocol conversion method, the model of which is finite state machine. KHLAAdaptor1516 allows developers to separate interoperable adaptors from stand-alone simulators. The interoperable adaptor manages mapping between HLA services and simulation messages for simulator, This separation increases robustness of a federation and reusability of simulators as well as alleviates much effort and time for maintenance.

A Design Method of Gateway for HLA based Simulation using Object Model (객체 모델을 이용한 HLA기반 시뮬레이션의 게이트웨이 설계 방법)

  • Shim, Jun-Yong;Lee, Yong-Heon;Kim, Sae-Hwan
    • Proceedings of the Korea Information Processing Society Conference
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    • 2011.11a
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    • pp.1334-1337
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    • 2011
  • HLA(High Level Architecture)는 분산 환경의 모델링 및 시뮬레이션(Modeling & Simulation)을 위한 공통 아키텍처를 제공하는 기술 표준이며, RTI(Run-Time Infrastructure)를 통해 HLA 서비스를 제공한다. HLA는 연동 객체 모델인 FOM(Federation Object Model)을 기반으로 시뮬레이션 환경을 구성하며, 시뮬레이션에 참여하는 모든 시뮬레이터는 동일한 FOM을 소유해야 한다. 따라서 시뮬레이션 체계 간 연동을 수행하기 위해서는 FOM을 통합하거나 FOM 간 연동을 위한 게이트웨이를 구현해야 한다. 한편, FOM을 통합하는 방법은 각 시뮬레이션의 연동 인터페이스 수정이 필요하기 때문에 게이트웨이를 구현하는 방법이 기존 시스템의 변경을 최소화할 수 있다. 따라서 본 논문은 HLA기반 시뮬레이션의 체계 간 연동을 제공할 수 있는 게이트웨이 구조를 제시한다. 특히, XML 형태의 객체 모델을 기반으로 교환 메시지를 정의하고, 메시지 처리 모듈을 게이트웨이에 플러그인 함으로써 시뮬레이션 체계 간 연동의 용이함을 보여준다.

Analysis of HLA in Patients with Obstructive Sleep Apnea Syndrome (폐쇄성 수면무호흡증후군 환자에서 사람백혈구항원 분석)

  • Lee, Sang Haak;Kim, Chi Hong;Ahn, Joong Hyun;Kang, Ji Ho;Kim, Kwan Hyoung;Song, Jeong Sup;Park, Sung Hak;Moon, Hwa Sik;Choi, Hee Baeg;Kim, Tai Gyu;Choi, Young Mee
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.3
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    • pp.298-305
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    • 2005
  • Background : Obstructive sleep apnea syndrome (OSAS) is believed to have multifactorial causes. The major risk factors for OSAS are obesity, narrowed upper airways, and abnormal cranial-facial structures. A genetic basis for OSAS has been also suggested by reports of families with many members affected. This study analyzed the HLA typing in patients with OSAS to determine the possible role of genetics in OSAS. Methods : Twenty-five Korean patients with OSAS (1 woman and 24 men; age range 30-66 years) were enrolled in this study. A diagnosis of OSAS was made using full-night polysomnography. The control group consisted of 200 healthy Korean people. Serologic typing of the HLA-A and B alleles was performed in all patients using a standard lymphocyte microcytotoxicity test. Analysis of the polymorphic second exons of the HLA-DRB1 gene was performed using a polymerase chain reaction-sequence specific oligonucleotide probe. Results : The allele frequency of HLA-A11 was significantly lower in patients with OSAS compared with the controls (p<0.05). The HLA-B allele frequencies in the patients and controls had a similar distribution. Analysis of the HLADRB1 gene polymorphisms showed an increased frequency of DRB1*09 in the OSA patients compared with the controls (p<0.05). When the analysis was performed after dividing the OSAS patients according to the severity of apnea, the allele frequency of HLA-DRB1*08 was significantly higher in the severe OSA patients (apnea index >45) than in the controls (p<0.05). Conclusion : This study revealed an association between OSAS and the HLA-A11 and DRB1*09 alleles as well as association between the disease severity and the HLA-DRB1*08 allele in Korean patients. These results suggest that genetics plays an important role in both the development and the disease severity of OSAS.

Immunoregulatory Function of HLA-G in Gastric Cancer

  • Tuncel, Tolga;Karagoz, Bulent;Haholu, Aptullah;Ozgun, Alpaslan;Emirzeoglu, Levent;Bilgi, Oguz;Kandemir, Emin Gokhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7681-7684
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    • 2013
  • Background: Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. Materials and Methods: We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. Results: There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival. Conclusions: We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.

Association between 14bp Insertion/Deletion Polymorphism in Exon 8 of HLA-G gene and Oral Squamous Cell Carcinoma in Korean Population

  • Kang, Sang Wook;Ban, Ju Yeon
    • International Journal of Oral Biology
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    • v.42 no.2
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    • pp.79-83
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    • 2017
  • Abnormal HLA-G expression occurs in various diseases such as melanoma, renal cell carcinoma, asthma, and classic Hodgkin's lymphoma. The purpose of this study was to determine whether HLA-G gene is linked with oral squamous cell carcinoma (OSCC). To investigate the possible link with susceptibility to OSCC, 54 OSCC patients and 120 healthy controls were enrolled in this study. HLA-G 14bp insertion/deletion polymorphism is in 3'-untranslated region of HLA-G gene. HLA-G 14bp insertion/deletion polymorphism was analyzed using the polymerase chain reaction (PCR) method. For the analysis of genetic data, SPSS18.0 program was used. Logistic regression models were performed for odds ratio (OR), 95 percent confidence interval (CI), and P value. There was a significant difference in distribution allele between OSCC patients and control subjects (OR=0.018, 95% CI=0.002-0.131, p<0.001). Our results suggest that HLA-G 14bp insertion/deletion polymorphism may be linked with susceptibility to OSCC in the Korean population.

Determination of HLA-A*02 Alleles Using Nested PCR-SSP in Korean Population

  • Lee, Kyung-Ok;Heo, Jeong-Ho-Ho;Kim, Hye-Jin;Lee, Eun-Mi;Hong, Sung-Hoi;Kim, Yoon-Jung
    • Animal cells and systems
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    • v.1 no.1
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    • pp.129-134
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    • 1997
  • HLA-A2 is one of the most diversified HLA-class I antigen with 17 subtypes so far identified at the molecular level. HLA-A*02 subtyping has significant implications on the tissue typing for organ and bone marrow transplantations. Recently, DNA-based typing methods have been successfully applied to the elucidation of HLA gene polymorphisms. In the present study, HLA-A*O2 genotyping was established by using nested polymerase chain reaction-sequence specific primers (PCR-SSP) and distribution of A*O2 alleles were determined in Korean individuals. Genomic DNA prepared from four B-lymphoblastoid cell lines and lymphocytes from serologically defined 48 HLA-A2 Korean individuals by phenol/chloroform extractions was typed. The results of the four B-lymphoblastoid cells were consistent with the previous data typed by PCR analysis. Five A*O2 alleles-A*0201, A*0203, A*0206, A*0207 and A*0210-were commonly observed in a total of 17 A*02 alleles. Of these, A*0207 (f=49.0%) was the most frequent allele in Korean population. A*0206 (f=28.3%) and A*0201 (f=17.0%) were also found frequently while A*0203 and A*0210 types were observed in less than 5%. In conclusion, the high level of discrimination for HLA-A*O2 alleles will prove useful and informative in the study of transplant survival, and may identify the importance of allelic differences not readily detectable by serology on host and donor compatibility.

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