• Genomics & Informatics
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• 제17권3호
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• pp.29.1-29.8
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• 2019

The Wellcome Trust Case Control Consortium (WTCCC) study was a large genome-wide association study that aimed to identify common variants associated with seven diseases. That study combined two control datasets (58C and UK Blood Services) as shared controls. Prior to using the combined controls, the WTCCC performed analyses to show that the genomic content of the control datasets was not significantly different. Recently, the analysis of human leukocyte antigen (HLA) genes has become prevalent due to the development of HLA imputation technology. In this project, we extended the between-control homogeneity analysis of the WTCCC to HLA. We imputed HLA information in the WTCCC control dataset and showed that the HLA content was not significantly different between the two control datasets, suggesting that the combined controls can be used as controls for HLA fine-mapping analysis based on HLA imputation.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제26권1호
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• pp.50-57
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• 2023

Purpose: The purpose of this study was to determine the pattern of human leukocyte antigen (HLA)-DQ genotype in children diagnosed with celiac disease (CD) (biopsy proven), and to compare this with a control group; and secondarily, to correlate HLA genotypes with clinical profiles of CD. Methods: This cross-sectional comparative observational study included 26 controls and 52 patients diagnosed with CD who presented at Sir Padampat Mother and Child Health Institute, Jaipur, from May, 2017 to October, 2018. HLA DQ genotype was assessed for each patients and correlated with clinical profiles. Results: HLA DQ2/DQ8 genotypes were significantly more common in CD (present in 100.0% cases) than in controls (23.1%) in Northern India (Rajasthan). When HLA DQ2.5 and DQ8 were present together, individuals had significantly more atypical presentations and severe findings on duodenal biopsy. Similarly, patients with the HLA DQ 2.5 genotype were also predisposed to more severe endoscopic findings, while HLA DQ2.2 predisposed them to less severe biopsy findings. HLA DQ8 was significantly associated with later age at diagnosis (>5 years) and shorter stature. The highest HLA DQ relative risk (RR) for CD development was associated with HLA DQ2.5 and DQ2.2 in combination, followed by HLA DQ2.5 and DQ8 in combination, while HLA DQx.5 and HLA DQ2.2 together had the lowest risk. Conclusion: HLA DQ2/DQ8 genotypes are strongly associated with pediatric CD patients in northern India. These genotypes and their combinations may be associated with different clinical presentations of CD, and may help predict severity of CD.

• Clinical and Experimental Reproductive Medicine
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• 제47권2호
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• pp.122-129
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• 2020

Objective: The survival of a semi-allogeneic fetus depends on several immunological mechanisms, and it has been suggested that recurrent pregnancy loss (RPL) could develop as a result of one or more immunological abnormalities. Methods: Compatibility between partners for human leukocyte antigen (HLA) genotypes and the relationships between maternal killer-cell immunoglobulin-like receptor (KIR) and paternal HLA-Bw4/Bw6 and HLA-C1/C2 supra-groups were investigated in 25 couples with RPL in comparison to healthy couples with children. HLA and KIR genotyping was performed using polymerase chain reaction with sequence-specific primers and/or sequence-specific oligonucleotides. Results: HLA class I incompatibility between partners, especially in HLA-B alleles, was more common in the RPL group (p= 0.01). HLA-C2 homozygosity was more frequent in the male partners of RPL couples than in other groups (p= 0.03). The KIR2DL5 gene frequency was significantly higher in both the female and male partners of RPL couples, whereas the KIR2DS3 gene frequency in male partners of RPL couples was significantly reduced (p= 0.03). The presence of KIR2DL3 in women with RPL was correlated with the presence of HLA-C2 alleles in their spouses (p= 0.03). Conclusion: Our data from a Turkish population suggest that male HLA-C2 homozygosity may play an important role in RPL. Additionally, an incidental match between male HLA-C2 and female HLA-C1 ligand KIR receptors might perturb the balance between activatory and inhibitory KIR-ligand interactions during pregnancy in couples affected by RPL. The roles of orphan KIR2DL5 and orphan KIR2DS3 in RPL remain obscure.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5399-5403
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• 2012

Aims and Background: Human leukocyte antigen-G and interleukin-2 receptor play pivotal roles in the proliferation of lymphocytes, and thus generation of immune responses. Their overexpression has been evidenced in different malignant hematopoietic diseases. This study aimed to validate serum soluble human leukocyte antigen-G (sHLA-G) and serum soluble interleukin-2 receptor (sIL-2R) as an additional tool for the diagnosis and follow up of acute lymphoblastic leukemia (ALL). Subjects and Methods: Both markers were determined by ELISA in the serum of 33 ALL pediatric patients before treatment and after intensification phase of chemotherapy as well as in the serum of 14 healthy donors that were selected as a control group. Results: ALL patients showed abnormal CBC and high serum lactate dehydrogenase, which were improved after chemotherapy. Also, there was a non-significant increase in serum sHLA-G in ALL patients compared with the control group. However, after chemotherapy, sHLA-G was increased significantly compared with before treatment. On the other hand, serum sIL-2R in ALL patients was increased significantly compared with the control group. After chemotherapy, sIL-2R decreased significantly compared with before treatment. Conclusions: From these results it could be suggested that measurement of serum sHLA-G might be helpful in diagnosis of ALL, while sIL-2R might be useful in diagnosis and follow-up of ALL in pediatric patients.

• Genomics & Informatics
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• 제15권3호
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• pp.108-111
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• 2017

Recently developed computational methods allow the imputation of human leukocyte antigen (HLA) genes using intergenic single nucleotide polymorphism markers. To improve the imputation accuracy in HLA imputation, it is essential to increase the sample size and the diversity of alleles in the reference panel. Our software, MergeReference, helps achieve this goal by providing a streamlined pipeline for combining multiple reference panels into one.

• Oncology Letters
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• 제41권5호
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• pp.2625-2635
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• 2019

The majority of natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy. The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. The role of NK cells is specifically regulated by the activating or inhibitory killer cell immunoglobulin-like receptors (KIRs) on their surface, which bind to the human leukocyte antigen (HLA) class I ligands present on the target cells. The association between KIR and HLA is derived from the diversity of KIR/HLA gene profiles present in different individuals, and this determines the cytotoxic effect of NK cells on cancer cells. Chronic myeloid leukemia (CML) is a hematological leukemia characterized by the hyper-proliferation of myeloid cells, with the majority of patients with CML presenting with abnormal immune cells. Tyrosine kinase inhibitors are the present standard therapy for CML, but are associated with numerous adverse side effects. Various studies have proposed CML therapy by immunotherapeutic approaches targeting the immune cells. This review summarizes the contents of NK cells and the association between KIR/HLA and leukemia, especially CML. This is followed by a discussion on the development of NK cell immunotherapy in hematological malignancies and research into strategies to enhance NK cell function for CML treatment.

• 대한임상검사과학회지
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• 제40권2호
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• pp.94-97
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• 2008

The human leukocyte antigen (HLA) is the name of the major histocompatibility complex (MCH) in humans. The superlocus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6. and encode cell surface antigen-presenting proteins and many other genes. HLA class I antigen (A, B & C) present peptides from inside the cell. These peptides are produced from digested proteins that are broken down in the lysozymes. Most expressed HLA loci exhibit a remarkable degree of allelic polymorphism, which derives from sequence differences predominantly localized to discrete hypervariable regions of the amino terminal domain of the molecule. In this sutdy, the HLA-A genotypes were determined in twenty students unrelated koreans using the PCR-SSP (Polymerase Chain Reaction-Sequence Specific Primer) technique. Several specific primer pairs in assigning the HLA-A gene were used (A*0201, A*33, A*2401). The results of PCR-SSP, the HLA-A*0201 primer was detected eleven (55%), the HLA-A*33 were detected seven (35%) and the HLA-A*2401 were detected seven (35%). This study shows that the PCR-SSP technique is relatively simple, fast and a practical tool for the determination of the HLA-A genotypes.

• 수면정신생리
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• 제4권1호
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• pp.89-95
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• 1997

The authors studied 5 cases of idiopathic CNS hypersomnia who visited Division of Sleep Studies, Seoul National University Hospital in 1995. Detailed medical history was taken and nocturnal polysomnography(NPSG), multiple sleep latency test(MSLT) and human leukocyte antigen(HLA) typing were performed. Neither cataplexy nor hypnagogic hallucination was reported in all cases and in NPSGs, there were tendencies of increased sleep period time and decreased slow wave sleep time. In MSLT, all the subjects showed average sleep latencies less than 8 minutes without sleep-onset rapid eye movement period(SOREMP). In HLA typing, some correlation between idiopathic CNS hypersomnia and HLA DR4 was observed. In contrast to previous reports, overall treatment response with methylphenidate was remarkable. Therefore, the authors suggest that patients suspected of idiopathic CNS hypersomnia be actively evaluated and treated with rather optimistic perspective.

• 수면정신생리
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• 제8권2호
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• pp.107-112
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• 2001

목 적 : 본 연구는 기면병 환자와 정상 대조군에서 사람 백혈구 항원(human leukocyte antigen, 이하 HLA) DQB1*0602와 DR2의 발현 빈도를 조사하여 한국인 기면병 환자의 표지자로서의 가능성을 확인하고자 하였으며, 동시에 기면병 환자에서 나타나는 증상의 특성을 조사하였다. 방 법 : 야간수면 다원검사 및 입면잠복기 반복검사에서 입면잠복기의 평균값이 5분 이하이며, 최소 2회 이상의 수면시작 REM기(sleep onset REM periods)가 발생한 기면병 환자 20명(남자 11명, 여자 9명, 연령분포 $8{\sim}55$세, 평균연령 $28.2{\pm}13.0$세)과 정상 대조군 21명(남자 9명, 여자 12명, 연령분포 $21{\sim}39$세, 평균연령 $28.6{\pm}4.4$세)을 대상으로 하여 HLA typing을 시행하였다. 기면병의 제반 임상증상은 면담과 수면설문지를 통하여 수집하였다. 결 과 : 1) 기면병 환자군의 입면잠복기 반복 검사 결과 입면잠복기의 평균값은 $2.4{\pm}2.0$분이었으며, Sleep onset REM periods의 발생 평균 회수는 $3.0{\pm}1.6$회로 나타났다. 2) 기면병 환자군 모두에서 기면병의 주요 증상인 과도한 주간 졸리움 및 탈력발작을 나타냈고, 수면마비, 입면환각 및 야간수면장애는 각각 12명(60.0%), 14명(70.0%) 및 15명(75.0%)에서 발생하였다. 3) 탈력발작은 주로 감정적인 자극에 의하여 유발되어, 웃을때(80%, n=16)와 농담할 때(70%, n=14)에 가장 흔하게 유발되었으며, 탈력발작 발생부위의 빈도는 무릎과 다리 부분이 95%(n=19)이었으며, 턱부위는 30%(n=6)로 나타났다. 4) HLA-DQB1*0602는 환자군 20명중 18명(90.0%), 정상 대조군 21명중 5명(23.8%)에서 양성으로 나타났으며, HLA-DR2는 환자군 중 18명(90%), 정상 대조군 중 7명 (35%)에서 양성으로 나타났다. 결 론 : 이상의 결과에서 한국인 기면병 환자에서 HLADQB1*0602 양성이 높은 빈도로 나타났으며, 여러 인종들을 대상으로 한 여러 연구 결과와도 일치하여 HLA-DQB1*0602가 인종을 초월한 매우 유용한 표지자가 될 수 있을 것으로 생각된다.

• Clinical and Experimental Pediatrics
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• 제54권7호
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• pp.313-315
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• 2011

Reactive arthritis comprises a subgroup within infection-associated arthritides in genetically susceptible hosts. Researchers and clinicians recognize two clinical forms of reactive arthritis which occurs after genitourinary tract infection and after gastrointestinal tract infection. Chlamydia infection has been implicated as the most common agent associated with post-venereal reactive arthritis. Studies have proposed Shigella infection, Salmonella infection, or Yersinia infection as the microorganisms responsible for the post-dysenteric form. The human leukocyte antigen (HLA)-B27 antigen is the best-known predisposing factor. We report a case of HLA-B27-associated reactive arthritis after Salmonella enteritis at Pusan National University hospital.