Human Leukocyte Antigen-DQ Genotyping in Pediatric Celiac Disease

Stuti Pareek,Raj Kumar Gupta,Abhinav Sharma,Sandhya Gulati 대한소아소화기영양학회 2023 Pediatric gastroenterology, hepatology & nutrition Vol.26 No.1

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.

한국 소아기 류마티스관절염 환자에서 Human Leukocyte Antigen-DRB1 대립유전자와의 연관성

이찬재 ( Chan Jae Lee ),손태영 ( Tae Young Sohn ),이대형 ( Dae Hyoung Lee ),이혜란 ( Hae Ran Lee ),김미영 ( Mi Young Kim ),김광남 ( Kwang Nam Kim ) 대한류마티스학회 2014 대한류마티스학회지 Vol.21 No.4

Objective. The aim of this study is to investigate the association of different subgroups of juvenile rheumatoid arthritis (JRA) with human leukocyte antigen (HLA) class II DR alleles. Methods. One hundred and nineteen Korean juvenile rheumatoid arthritis patients were classified as HLA-DRB1 allele. To assess the frequency, phenotype frequencies of all JRA cases and each subtypes were compared to those of 485 adult controls. Results. HLA-DRB1*01 was associated with increased risk of JRA. Furthermore, DRB1*01 was associated with polyarticular JRA and pauciarticular JRA. The frequencies of DRB1*14 and DRB1*15 were higher in systemic JRA patients than the controls. Conclusion. The data of this study on Korean children with JRA suggests that HLA-DRB1*01 was associated with the susceptibility of JRA. The study should be extended to include larger numbers of patients.

Immunologic properties of differentiated and undifferentiated mesenchymal stem cells derived from umbilical cord blood

Hyo-Jong Lee,Kyung-Sun Kang,Sun-Young Kang,Hyung-Sik Kim,Se-Jin Park,Seung-Yong Lee,Won Young Paik,Lyon Lee,Seongchan Yeon,Ji Kwon Park,Kwang-Dong Kim,Hee-Chun Lee 대한수의학회 2016 Journal of Veterinary Science Vol.17 No.3

The expression of immunogenic markers after differentiation of umbilical cord blood (UCB)-derived mesenchymal stem cells (MSC) has been poorly investigated and requires extensive in vitro and in vivo testing for clinical application. The expression of human leukocyte antigen (HLA) classes on UCB-derived MSC was tested by Fluorescence-activated cell sorting analysis and immunocytochemical staining. The undifferentiated MSC were moderately positive for HLA-ABC, but almost completely negative for HLA-DR. The MSC differentiated to chondrocytes expressed neither HLA-ABC nor HLA-DR. The proliferation of MSC was not significantly affected by the allogeneic lymphocytes stimulated with concanavalin A. The responder lymphocytes showed no significant decrease in proliferation in the presence of the MSC, but the apoptosis rate of the lymphocytes was increased in the presence of MSC. Taken together, these findings indicate that UCB-derived MSC differentiated to chondrocytes expressed less HLA class I and no class II antigens. The MSC showed an immunomodulatory effect on the proliferation and apoptosis of allogeneic lymphocytes. These data suggest that the differentiated and undifferentiated allogeneic MSC derived from umbilical cord blood can be a useful candidate for allogeneic cell therapy and transplantation without a major risk of rejection.

Successful treatment of early acute antibody-mediated rejection in an human leukocyte antigen-incompatible and ABO-incompatible living-donor kidney transplant patient

Sujin Gang,Ahram Han,Sang-il Min,Jongwon Ha,Jaeseok Yang 대한이식학회 2019 Korean Journal of Transplantation Vol.33 No.4

For successful human leukocyte antigen-incompatible (HLAi) or ABO-incompatible (ABOi) living-donor kidney transplantations (LDKTs), pretransplant desensitization is essential; however, early antibody-mediated rejection (ABMR) remains the most important complication after HLAi or ABOi transplantation. Here, we report a case of early acute ABMR in simultaneous HLAi and ABOi LDKT with preformed donor-specific antibody (DSA), despite desensitization. Dialysis-dependent, severe ABMR occurred with a rebound of pre-existing DSA and appearance of de novo DSA after initial normalization of renal function, 8 days postoperatively. However, a low anti-ABO antibody titer (1:8) was maintained after transplantation. Combination therapy of plasmapheresis, high-dose intravenous immunoglobulin, and bortezomib improved both ABMR and renal functions. Thus, an appropriate preventive and therapeutic management for early ABMR is important among high-risk LDKT patients. Furthermore, early AMBR can occur despite pretransplant desensitization as seen in this case, and close monitoring of the patient and prompt management are considered vital for better therapeutic outcomes.

Clinical significance of the presence of anti-human leukocyte antigen-donor specific antibody in kidney transplant recipients with allograft dysfunction

( Byung Ha Chung ),( Jeong Ho Kim ),( Bum Soon Choi ),( Cheol Whee Park ),( Ji-il Kim ),( In Sung Moon ),( Yong-soo Kim ),( Yeong Jin Choi ),( Eun-jee Oh ),( Chul Woo Yang ) 대한내과학회 2018 The Korean Journal of Internal Medicine Vol.33 No.1

Background/Aims: This study investigated the clinical significance of detecting anti-human leukocyte antigen-donor specific antibody (HLA-DSA) in kidney transplant recipients (KTRs) requiring indication biopsy owing to allograft dysfunction. Methods: We analyzed the presence of HLA-DSA in 210 KTRs who took indication biopsy. We divided these cases into two groups, HLA-DSA (+) (n = 52) and HLA-DSA (-) (n = 158) group, and compared the clinical characteristics, pathological findings, and clinical outcomes of the two groups. Results: The rates of retransplant, pretransplant sensitization, and HLA-mismatch were significantly higher in HLA-DSA (+) group than in HLA-DSA (-) group (p < 0.05 for each comparison). In histologic finding, all types of rejections were more frequent in the former group. Besides, scores of both the T-cell injury markers such as tubulitis, interstitial inflammation, and vasculitis and antibody-mediated injury markers such as peritubular C4d deposition and microvascular inflammation (glomerulitis plus peritubular capillaritis) were higher in HLA-DSA (+) group (p < 0.05 for each). Notably, allograft outcomes were worse in HLA-DSA (+) group. Further, multivariate analysis showed that presence of HLA-DSA, advanced interstitial fibrosis/tubular atrophy (interstitial fibrosis plus tubular atrophy ≥ 2), and allograft rejection in biopsy were independent risk factors for allograft failure. Conclusions: The results of this study showed that presence of HLA-DSA in a case of allograft dysfunction adversely influences allograft outcome, and its detection, irrespective of the result of the allograft biopsy, necessitates intensive monitoring and treatment.

Serum Human Leukocyte Antigen-G and Soluble Interleukin 2 Receptor Levels in Acute Lymphoblastic Leukemic Pediatric Patients

Motawi, Tarek M.K.,Zakhary, Nadia I.,Salman, Tarek M.,Tadros, Samer A. Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.11

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.

HLA-B27 연관 앞포도막염의 형광안저혈관조영술 소견과 포도막염 재발과의 관련성

이종섭(Jong Sub Lee),류소정(So Jung Ryu),이병로(Byung Ro Lee),안성준(Seong Joon Ahn) 대한안과학회 2021 대한안과학회지 Vol.62 No.10

목적: HLA-B27 연관 앞포도막염의 형광안저혈관조영술 소견과 재발의 관련성을 연구하였다. 대상과 방법: 최초로 진단 받고 치료를 시작한 HLA-B27 연관 앞포도막염 환자 중 형광안저혈관조영술을 시행한 56명(56안)의 의무기록을 후항적으로 검토하였다. 형광안저혈관조영술상 시신경유두누출, 주변부혈관누출 유무와 초진 시 전방염증의 정도, 1년 내 재발과의 관련성, 재발까지의 시기에 영향을 미치는 요인과의 연관성에 대해 분석하였다. 결과: 총 56명(56안)의 환자 중 시신경유두누출이 발견된 경우는 23명(41.1%), 주변부혈관누출이 발견된 경우는 36명(64.3%)이었다. 시신경유두누출(p=0.841) 혹은 주변부혈관누출(p=0.775)과 전방염증의 정도는 유의한 관계를 보이지 않았다. 시신경유두누출이 있는 군의 1년 내 재발은 14명(60.9%), 없는 군의 1년 내 재발은 11명(33.3%)으로 두 군은 유의한 차이를 보였다(p=0.041). 반면 주변부혈관누출이 있는 군의 1년 내 재발은 19명(52.8%), 없는 군의 1년 내 재발은 8명(40.0%)으로 유의한 차이를 보이지 않았다(p=0.602). 하지만 첫 재발까지의 기간에 대해 나이(p=0.772), 전방염증 정도(p=0.841), 시신경유두누출(p=0.108), 전신 스테로이드 사용 여부(p=0.321)는 유의한 상관관계를 보이지 않았다. 결론: HLA-B27 연관 앞포도막염에서 형광안저혈관조영술상 누출과 1년 내 재발 여부 및 재발까지의 기간 사이의 관계를 확인하였다. 시신경유두누출이 있는 경우 1년간 면밀한 경과 관찰을 통해 재발 여부를 확인해야 할 것으로 생각된다. Purpose: To evaluate the associations of fluorescein angiographic findings with recurrence of human leukocyte antigen (HLA)-B27-associated anterior uveitis. Methods: Medical records of 56 eyes of 56 patients with first-onset, treatment-naive HLA-B27-associated anterior uveitis who performed fluorescein angiography was analyzed. We recorded the fluorescein angiographic findings of optic disc and peripheral vascular leakage and anterior chamber inflammation at the first visit. The 1-year recurrences and times to the first recurrences and the associations between them were investigated. Results: Fluorescein angiography revealed optic disc leakage in 23 patients (41.1%) and peripheral vascular leakage in 36 (64.3%). We found no significant association between the anterior chamber inflammation grade and either optic disc (p = 0.841) or peripheral vascular (p = 0.775) leakage. The 1-year recurrence rate in the optic disc leakage-positive group was significantly higher than in the leakage-negative group (14 patients, 60.9% vs. 11 patients, 33.3%) (p = 0.041), but peripheral vascular leakage status did not significantly affect the recurrence rate (19 leakage-positive patients, 52.8% vs. 8 leakage-negative patients, 40.0%) (p = 0.602). The time to first recurrence was not significantly associated with age (p = 0.772), anterior chamber inflammation (p = 0.841), optic disc leakage (p = 0.108), or systemic corticosteroid use (p = 0.321). Conclusions: We sought correlations between angiographic leakage in patients with HLA-B27-associated anterior uveitis, and the 1-year recurrence rate and the time to first recurrence. Careful follow-up for at least 1 year after initial diagnosis is essential to monitor possible recurrence in patients with optic disc leakage. J Korean Ophthalmol Soc 2021;62(10):1364-1369

FAT10 Induces cancer cell migration by stabilizing phosphorylated ABI3/NESH

엄효진,정호임,이범구,김예린,이지현,노종성,이승근,박혜련,William H. Robinson,손동현 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

The WAVE regulatory complex (WRC) is involved in various cellular processes by regulating actinpolymerization. The dysregulation of WRC components is associated with cancer development. ABI family member 3 (ABI3)/new molecule including SH3 (NESH) is one of the WRC componentsand it has been reported that ABI3 phosphorylation can affect WRC function. Although severalresidues of ABI3 have been reported to be possible phosphorylation sites, it is still unclearwhich residues are important for the function of ABI3. Furthermore, it is unclear how thephosphorylated form of ABI3 is regulated. Here, we demonstrate that ABI3 is stabilized by itsinteraction with human leukocyte antigen-F adjacent transcript 10 (FAT10). Using phospho-deador phospho-mimetic mutants of ABI3, we showed that serine 213 and 216 are importantphosphorylation sites of ABI3. In particular, FAT10 has a higher affinity for the phosphorylatedform of ABI3 than the non-phosphorylated form, and it stabilizes the phosphorylated form morethan the non-phosphorylated form through this differential affinity. The interaction betweenFAT10 and the phosphorylated form of ABI3 promoted cancer cell migration. Therefore, ourresults suggest that FAT10 stabilizes the phosphorylated form of ABI3, which may lead to WRCactivation, thereby promoting cancer cell migration.

한국인의 메니에르병의 병인에 대한 인체백혈구항원의 영향

여상원,박시내,전은주,이흥엽,박용수,서병도 대한이비인후과학회 2002 대한이비인후과학회지 두경부외과학 Vol.45 No.2

Background and Objectives:This study was designed to investigate the influence of human leukocyte antigen (HLA) on genetic susceptibility to Menieres disease and to evaluate the correlation betwen HLA genotypes and results of examination for various clinical factors of Menieres disease. Materials and Method:39 patients with MD and 199 healthy controls. For HLA-A and B, the serologic typing was performed according to a standard microlymphocytotoxicity technique. The HLA-C typing was performed by the ARMS-PCR method at DNA level. Results:The frequencies of HLA-Cw*0303 (RR=2.5, p<0.02), and Cw*0602 (RR=3.7, p<0.03) were significantly increased in patients with Menieres disease, when compared to the controls. However, HLA-B44 (RR=0.2, p< ) and Cw*0102 (RR=0.3, p<0.03) were significantly decreased in the patients compared to the controls. When an association between hearing level and the presence of HLA alles was evaluated, the frequencies of HLA-B13 (RR=7.4, p<0.004), Cw*0303 (RR=4.5, p<0.02) and Cw*0602 (RR=6.5, p<0.02) (RR=0.1, p<0.02) and Cw*0102 (RR=0.1, p<0.03) were significantly decreased in patients with the state of mild to profound hearing losses, compared to the controls. HLA-B13 showed a different distribution pattern betwen patients with and without hearing losses. Conclusion:These results suggest that some HLA alleles may be useful genetic markers in conferring the susceptibility to Menieres disease and in implying a prognosis in Korean patients. (Korean J Otolaryngol 2002;45:114-7)

<i>MICB</i> polymorphisms and haplotypes with <i>MICA</i> and HLA alleles in Koreans

Cha, C.‐,H.,Sohn, Y.‐,H.,Oh, H.‐,B.,Ko, S.‐,Y.,Cho, M.‐,C.,Kwon, O.‐,J. Blackwell Publishing Ltd 2011 Tissue antigens Vol.78 No.1

<P>Major histocompatibility complex (MHC) class I chain‐related gene B (<I>MICB</I>) is located within the human MHC class I region. The location of <I>MICB</I> in the MHC region may imply the presence of linkage disequilibrium with polymorphic <I>MICA</I> and human leukocyte antigen (HLA) loci. <I>MICB</I> is also polymorphic; however, <I>MICB</I> polymorphisms have not been investigated in Koreans. Using sequence‐based typing (SBT), we estimated the allelic frequencies of <I>MICB</I> and haplotypes with <I>MICA</I>, <I>HLA‐B</I>, and <I>HLA‐DRB1</I> at high resolution in a population of 139 unrelated Korean individuals. Eight <I>MICB</I> alleles were identified. The most frequent allele was <I>MICB*005:02/*010</I> (57.2%), followed by <I>*002</I> (11.5%), <I>*004</I> (8.3%), <I>*005:03</I> (8.3%), and <I>*008</I> (6.8%). The most common two‐locus haplotypes were <I>MICB*005:02/*010‐MICA*010</I> (19.4%), <I>MICB*005:02/*010‐DRB1*15:01</I> (6.5%), and <I>MICB*005:02/*010‐B*15:01</I> (10.4%); the most common three‐locus haplotypes were <I>B*15:01‐MICA*010‐MICB*005:02/*010</I> (5.8%) and <I>MICA*010‐MICB*005:02/*010‐DRB1*04:06</I> (10.4%); and the most common four‐locus haplotype was <I>B*15:01‐MICA*010‐MICB*005:02/*010‐DRB1*04:06</I> (5.8%). This is the first study to provide information about <I>MICB</I> allele frequencies and haplotypes with HLA in Koreans. These study results should help understand mechanisms of disease association between the <I>MICB</I> locus and neighboring loci in Koreans.</P>