Search

Postherpetic neuralgia (PHN), the most frequent complication of varicella-zoster virus reactivation, is characterized by pain that persists for more than 3 months, often for years after healing of zoster rash. A few studies revealing the association of human leukocyte antigen (HLA) with PHN have been reported, but only in the Japanese. The aim of this study was to investigate the primary HLA locus associated with PHN susceptibility in Koreans. We compared HLA-A, -B, -C, and DRB1 genotypes of 66 PHN patients with those of 54 herpes zoster (HZ) patients without developing PHN and 235 healthy controls. Frequencies of HLA-B*13, B*44, B*15 (B75), DRB1*10:01, and DRB1*12:02 were increased, and those of HLA-C*01, C*12, and DRB1*01:01 were decreased in PHN patients compared to those in controls (each, p < 0.05). Among these alleles, only the frequency of HLA-B*44 was significantly increased in PHN patients compared to that in HZ patients and the change was due to HLA-B*44:03 (PHN vs controls, p = 0.043; PHN vs HZ, p = 0.012). The results suggest that HLA-B*44:03 or other closely linked gene of the major histocompatibility complex is associated with susceptibility to the development of PHN after HZ, but not with the onset of HZ., (© 2016 APMIS. Published by John Wiley & Sons Ltd.)

Background: Fetal-maternal microchimerism (MC) can develop during pregnancy and may persist for decades. Pretransplantation fetal-maternal MC may be present between mother and child and between siblings; however, its effect on renal transplantation is not known. We investigated the effects of pretransplantation MC on allograft outcomes in human leukocyte antigen (HLA)-haploidentical family donor transplantation., Methods: A total of 106 cases transplanted from 1996 to 2004 were retrospectively studied, with median follow-up of 96 months. The study and control groups included 63 and 43 cases of HLA-haploidentical and HLA-identical donor transplantations, respectively. MC against mismatched donor HLA-DRB1 allele was detected in the recipient's peripheral blood using nested polymerase chain reaction-single-strand conformation polymorphism method. The allograft outcomes of HLA-haploidentical MC (+) and (-) subgroups were compared with those of HLA-identical group., Results: Pretransplantation MC in the HLA-haploidentical recipients was detected in 22.2% (14 of 63). Compared with HLA-identical group, MC (-) subgroup showed significantly inferior allograft outcomes: higher acute rejection rate (11.6% vs. 42.9%; P=0.001), higher 5-year serum creatinine level (1.1 vs. 1.4 mg/dL; P=0.009), and lower 10-year rejection-free survival rate (83.7% vs. 54.5%; log-rank P=0.001). In contrast, MC (+) subgroup showed no significant differences from HLA-identical group in acute rejection rate (14.3%), 5-year serum creatinine level (1.1 mg/dL), and 10-year rejection-free survival rate (85.7%). Multivariate analysis revealed that pretransplantation MC is associated with a significantly lower risk of acute rejection (odds ratio=0.10; P=0.021)., Conclusion: Pretransplantation MC present in the recipient may have beneficial effects on rejection-free allograft survival in renal transplantation.

The main purpose of this report is to provide baseline gene frequencies of Knops blood group in the complement receptor 1 gene (CR1) in Korean population. In addition, possible relationship between the CR1 polymorphism and HLA specificities were studied, because the two systems had principal importance in immunity. CR1, which contains Knops antigens, was investigated by PCR-direct sequencing from 238 cord blood from Koreans. HLA data was archived from the enrolled cord blood units. Among the 7 SNPs, only 4843 (for KCAM antigen) and 4223 (for Yk(a)) nucleotide positions showed polymorphism. The genotype frequencies of KCAM were A/A (62.2%), A/G (33.2%), and G/G (4.6%); Yk(a) were C/C (29.4%), C/T (50%), and T/T (20.6%). KCAM (A/A) associated with HLA-DRB1(∗)13 (p=0.003, P(c)=0.0513); KCAM (G/G) with HLA-A(∗)30 (p<0.001, P(c)=0.0012). The Knops blood group system in Korean population has no diversity, except SNPs for KCAM and Yk(a), and the genotype of KCAM related with specific HLA alleles., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

We hypothesized that polymorphisms of the vitamin D receptor (VDR) gene might affect clinical outcomes of allogeneic hematopoietic stem cell transplantation (HSCT). Three VDR gene polymorphisms (BsmI G>A, ApaI G>T, and TaqI T>C) were genotyped in 147 patients who underwent HLA-matched sibling allogeneic HSCT. Frequencies of infection, graft-vs.-host disease (GVHD), overall survival (OS), and disease-free survival (DFS) were compared according to genotypes and haplotypes. Infection and acute GVHD had trends to be less frequent in patients with ApaI TT genotype than non-TT genotypes (p = 0.061 and p = 0.059, respectively). For TaqI genotypes, there were no statistical differences in frequency of infection and acute GVHD (p = 0.84 and p = 0.30, respectively), but TC genotype was associated with longer OS and DFS than TT genotype (p = 0.022 and p = 0.038, respectively). In the ApaI-TaqI haplotype analysis, patients with TC haplotype had significantly longer OS and DFS than those without TC haplotype (p = 0.022 and p = 0.038, respectively). In multivariable analysis, TaqI genotype and ApaI-TaqI haplotype of recipients were independent prognostic factors for both OS and DFS. This study suggests that the genotype and haplotype of VDR in recipient might be associated with clinical outcome of sibling HLA-matched HSCT., (© 2011 John Wiley & Sons A/S.)

Loss of heterozygosity (LOH) in chromosome 6p has been reported in a number of tumors and some hematologic malignancies, including ALL. LOH in chromosome 6p, on which the HLA genes are located, can give rise to false homozygosity results in HLA genotyping of patients with hematologic malignancies. Here we report false homozygosity results in HLA genotyping due to the loss of whole chromosome 6 in the neoplastic cells of a patient with ALL. A 33-yr-old Korean female patient was admitted for the evaluation of leukocytosis detected during a workup for headache. Her initial white blood cell count was 336.9×10(9)/L with 84% of blasts in the differential count. Precursor-B lymphoblastic leukemia was diagnosed from a subsequent bone marrow study. HLA high-resolution genotyping of the patient was requested at the time of diagnosis for possible hematopoietic stem cell transplantation. Homozygosity results (A(*)02:01, B(*)54:01, C(*)08:01, DQB1(*)04:01) were obtained, except for the DRB1 locus (DRB1(*)04:05, DRB1(*)11:01), in sequence-based typing. Conventional karyotyping of bone marrow metaphase cells revealed chromosomal abnormalities, with loss of multiple chromosomes including chromosome 6, and reduplication of the remaining chromosomes: 29,X,+X,+8,inv(9)(p11q13),+10,+14,+18,+21[15]/58,idemX2[3]/46,XX,inv(9)[2]. LOH at the HLA region was suspected and HLA genotyping was repeated with the peripheral blood in remission state after induction chemotherapy. All 5 HLA loci were typed as heterozygous (A(*)02:01, A(*)02:06, B(*)40:01, B(*)54:01, C(*)03:04, C(*)08:01, DRB1(*)04:05, DRB1(*)11:01, DQB1(*)03:01, DQB1(*)04:01). To avoid false HLA typing results in patients with hematologic malignancies, clinicians, as well as laboratory personnel, need to be aware of such problems and take appropriate precautions.

Background: In unrelated hematopoietic stem cell transplantation, the accuracy of HLA registry typing (RT) of donors is important for timely search and coordination of HLA-matched donors. We analyzed discrepancies between HLA RT and confirmatory typing (CT) results of stem cell donors in Korean and foreign registries., Methods: We analyzed the HLA typing results of 834 donors for whom CT was performed at Seoul National University Hospital between April 1997 and March 2010. For CT, DNA typing was used in majority of the cases and HLA-A and HLA-B serological typing was used in some early cases. The discrepancies between the typing results were analyzed at the serological/generic level., Results: The overall discrepancy rate (RT error rate) was 3.2%, and the rate was similar in the Korean and foreign registries. The discrepancy rates in the Korean and foreign registries were more than 10% in the 1997-2001 searches, but decreased to less than 3% in the 2002-2010 searches. Analysis of 19 cases of RT errors in the Korean registry revealed 3 cases of sample switchover errors and 16 cases of typing errors in one of the HLA-A, HLA-B, or HLA-DR loci. The RT error rate in Japan Marrow Donor Program was lower than those in other foreign registries., Conclusions: The error rate of HLA RT results of unrelated stem cell donors in the Korean registry was similar to those in the foreign registries, and has decreased in the recent searches following the change in the typing method from serological to DNA typing.

Heat shock protein 70-hom (HSP70-hom) plays an important role in protein folding and immune responses. Therefore, HSP70-hom gene polymorphisms may act as important factors in predicting the prognosis of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). To evaluate the role of HSP70-hom gene polymorphisms in the prognosis of patients receiving sibling human leukocyte antigen (HLA)-matched allogeneic HSCT, the HSP70-hom polymorphisms, T2437C and G2763A, were genotyped in 147 patients receiving sibling HLA-matched allogeneic HSCT. Individual diplotypes were estimated from genotype data of the two HSP70-hom polymorphisms using the expectation maximization algorithm. Patients with the 2763GG or GA genotype showed longer overall survival compared with those with the 2763AA genotype, and patients with a TG haplotype (TG/TA, TG/TG or TG/CG) also showed longer overall survival compared with those with a non-TG haplotype (TA/TA or TA/CG) (both G2763A genotype and diplotype, p<0.01). Moreover, the 2437TT genotype was found to be protective for treatment-related death compared with the 2437TC genotype, and a TG haplotype was found to be very protective for treatment-related death compared with a non-TG haplotype (T2437C genotype, p=0.04; and diplotype, p=0.02). Therefore, our results suggest that HSP70-hom polymorphisms play an important role in the prognosis of patients receiving sibling HLA-matched allogeneic HSCT., (© 2009 John Wiley & Sons A/S.)

Human leukocyte antigen (HLA) gene region encodes a set of HLA molecules functioning critical roles in immune response. Each HLA gene locus shows extensive polymorphism with ever-increasing number of alleles. The HLA nomenclature system for alleles defined by DNA typing was first established in 1987 and has been revised several times. Recently, it has been revised again with a new frame that can accommodate ever-increasing number of new alleles. The new system has also introduced the novel suffixes, P and G, to simplify reporting of ambiguous strings of alleles in typing reports. This review introduces the HLA nomenclature system-2010 in conjunction with its clinical application in Koreans.

For human embryonic stem cells (hESCs) to be used clinically, it is imperative that immune responses evoked by hESCs and their derivates after transplantation should be prevented. Human leukocyte antigens (HLA) and ABO blood group antigens are important histocompatibility factors in graft rejection. HLA matching between recipient and unrelated donors, in particular, is important in improving outcomes in hematopoietic cell transplantation (HCT). We have established and successfully maintained 29 hESC lines and analyzed the HLA and ABO genotypes of these lines. HLA-A, -B, -C and -DR (DRB1) genotyping was performed by polymerase chain reaction (PCR) sequence-based typing and ABO genotyping was carried out by PCR restriction fragment length polymorphism methods. To determine what proportion of the Korean population would be covered by these cell lines in organ transplantation, 27 cell lines with HLA-A, -B, and -DR data were evaluated for HCT (cord blood) donors and 28 cell lines with HLA-DR and ABO data were evaluated for solid organ (kidney) transplantation donors, and then compared the data with those from 6,740 donated cord bloods. When 2 HLA mismatches are allowed for HCT, as currently accepted for cord blood transplantation, it was estimated that about 16% and 25% of the possible recipients can find one or more donor cell lines with ≤2 mismatches at A, B, DRB1 allele level and at A, B antigen/DRB1 allele level, respectively. When HLA-DR antigen level matching and ABO compatibility was considered for solid organ (kidney) transplantation, it was estimated that about 29% and 96% of the possible recipients can find one or more ABO-compatible donor cell lines with 0 and 1 DR mismatches, respectively. We provided the first report on the HLA and ABO genotypes of hESC lines, and estimated the degree of HLA and ABO matching in organ transplantation for the Korean population.

Background: Majority of immune-mediated platelet refractoriness is caused by HLA alloimmunization and can be effectively managed by HLA-matched platelet transfusions. However, HLA class I-typed large-sized donor registry has not been well established in Korea. We evaluated the effectiveness of platelet transfusion using HLA crossmatch-compatible donors without HLA typing., Methods: Sixteen patients showing platelet refractoriness to random donor platelets (1 hr corrected count increment [CCI] <7,500/microL/m(2)) and HLA alloimmunization (class I panel reactive antibody >60%) were crossmatched with 78 platelet apheresis-eligible donors using National Institute of Health (NIH) and anti-human globulin (AHG) lymphocytotoxicity methods. NIH negative/AHG negative and NIH negative/AHG positive donors were selected as best and second choice donors, respectively., Results: Eleven patients (11/16, 69%) could find NIH-crossmatch negative donors and 27 donors (27/78, 35%) belonged to the best donors. To 8 patients, 32 apheresis platelet products from 19 donors were transfused. The mean 1 hr and 24 hr CCI values from the best donors were significantly higher than those from random donors (17,893 vs 2,358, P=0.003; 8,292 vs -614, P<0.001), whereas such differences were not observed for those from the second choice donors. Platelet storage time was inversely correlated with CCI values and platelets stored < or =10 hr after collection gave significantly higher CCI values. Neither ABO match nor donor status (related vs unrelated) affected the transfusion effectiveness., Conclusions: Effective post-transfusion platelet increment using HLA crossmatch-compatible donors was attained in patients with platelet refractoriness due to HLA antibodies, and this method can be used effectively where HLA-typed platelet donor registry is not available.