OBJECTIVETo study the genetic polymorphisms of human leukocyte antigen (HLA)- A, B, C, DRB1, DQA1, DQB1, DPA1and DPB1among ethnic Hans from southern China.

METHODS481 randomly selected individuals were genotyped using a polymerase chain reaction (PCR) sequence-based typing (SBT) method for the above genes. Their allele frequencies were determined by direct counting.

RESULTSIn total, 28 HLA-A, 57 HLA-B, 28 HLA-C, 40 HLA-DRB1, 18 HLA-DQA1, 17 HLA-DQB1, 6 HLA-DPA1and 21 HLA-DPB1alleles were identified. Among these, common alleles (with allelic frequencies > 0.05) included A*1101, A*2402, A*0207, A*3303, A*0201, B*40:01, B*46:01, B*58:01, B*13:01, B*15:02, C*01:02, C*07:02, C*03:04, C*03:02, C*08:01, C*03:03, C*04:01, DRB1*09:01, DRB1*15:01, DRB1*12:02, DRB1*08:03, DRB1*03:01, DRB1*04:05, DRB1*11:01, DQA1*01:02, DQA1*03:02, DQA1*03:03, DQA1*06:01, DQA1*01:03, DQA1*05:05, DQA1*01:04, DQA1*03:01, DQA1*05:01, DQB1*03:01, DQB1*03:03, DQB1*06:01, DQB1*05:02, DQB1*03:02, DQB1*02:01, DQB1*03:02, DQB1*06:02, DPA1*02:02, DPA1*01:03, DPA1*02:01, DPB1*05:01, DPB1*02:01, DPB1*13:01, DPB1*04:01and DPB1*02:02.For each of the locus, the overall frequencies of common alleles were 75.57%, 52.81%, 78.28%, 62.16%, 86.70%, 77.23%, 95.32% and 81.59%, respectively.

CONCLUSIONThe allelic frequencies of the 8 selected HLA loci among ethnic Hans from southern China may served as a reference for anthropology, legal medicine, transplantation and disease association studies.

Alleles ; Asian Continental Ancestry Group ; genetics ; China ; Gene Frequency ; Genotype ; Genotyping Techniques ; methods ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; HLA-C Antigens ; genetics ; HLA-DP Antigens ; genetics ; HLA-DQ alpha-Chains ; genetics ; HLA-DQ beta-Chains ; genetics ; HLA-DRB1 Chains ; genetics ; Histocompatibility Antigens Class I ; genetics ; Histocompatibility Antigens Class II ; genetics ; Humans ; Linkage Disequilibrium ; Polymerase Chain Reaction ; Polymorphism, Genetic

Human Leukocyte Antigen (HLA) typing of large groups of patients with various autoimmune diseases has demonstrated that some HLA alleles occur at higher frequencies in specific diseases than in the general population. Chronic urticaria has been shown to have an autoimmune basis by a previous study which found an association between chronic urticaria and specific HLA groups. We investigated the HLA subtypes of Turkish chronic urticaria patients. For this purpose 42 Turkish patients with chronic urticaria and 115 healthy controls were typed for HLA-DR and DQ by PCR-SSP (Polymerase Chain Reaction Sequence Specific Primers) low resolution DNA technique. We found an increased frequency of DR4 (42.9%, p=0.01) in chronic urticaria patients in comparison with that in healthy controls. This study supports the hypothesis that HLA alleles may be involved in the pathogenesis of chronic urticaria and that they appear to be directly involved in the initiation of the immune response.
Chronic Disease ; HLA-DQ Antigens/genetics ; HLA-DR Antigens/genetics ; HLA-DR4 Antigen/genetics ; Histocompatibility Antigens Class II/*genetics ; *Histocompatibility Testing ; Human ; Urticaria/*genetics/*immunology

OBJECTIVETo analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients.

METHODSHLA high-resolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out.

RESULTSForty-four HLA-A alleles were detected, and among them the frequencies of A*1101, A*2402, A*0201, A*0207, A*3303, A*0206 and A*3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and the frequencies of B*4001, B*4601, B*5801, B*1302 and B*5101 exceeded 0.05, and accounted for 43.0% of total. There were 44 HLA-Cw alleles, among them the frequencies of Cw*0702, Cw*0102, Cw*0304, Cw*0801, Cw*0602, Cw*0303, Cw*0302 and Cw*0401 exceeded 0.05, and were 80.3% of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1*0901, DRB1*1501, DRB1*1202, DRB1*0803, DRB1*0701, DRB1*0405, DRB1*0301 and DRB1*1101 exceeded 0.05, and were 70.1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1*0301, DQB1*0303, DQB1*0601, DQB1*0602, DQB1*0202, DQB1*0302, DQB1*0401, DQB1*0502 and DQB1*0201 exceeded 0.05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P > 0.05); but HLA-Cw and HLA-DQB1 loci did not (P < 0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24.6% of recipients found single HLA allele mismatched donors (9/10); 26.3% of recipients had two HLA alleles mismatched donors (8/10).

CONCLUSIONThe characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.

China ; ethnology ; Gene Frequency ; Genetics, Population ; HLA-A Antigens ; genetics ; HLA-B Antigens ; genetics ; HLA-C Antigens ; genetics ; HLA-D Antigens ; genetics ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Antigens Class I ; genetics ; Histocompatibility Testing ; Humans ; Tissue Donors

HLA-DR antigen and gene frequencies were studied in 150 unrelated Koreans in Seoul. HLA-DR4 was the most common DR specificity encountered and HLA-DR1 and -DR3 occurred with the lowest frequencies. The frequency of HLA-DR blank allele was 27.1%. HLA-B:DR haplotypes involving positive delta values differing significantly from zero were DR1:B7, DR2:Bw22, DR3:B17, DR5:Bw35, DRw6:B17, DR7:B12, DR7:B13, and DRw8:Bw16. The supertypic groups (MT1, MT2 and MT3) differ somewhat in frequencies from Other populations. These findings suggested that the Korean population, while having many similarities in HLA-DR antigen frequencies with those of neighboring Orientals, has not only different features in the distribution of HLA-DR antigens but also has unique HLA-B:DR haplotypes.
Gene Frequency ; HLA Antigens/analysis* ; HLA-B Antigens ; HLA-DR Antigens ; Haploidy ; Histocompatibility Antigens Class II/analysis* ; Human ; Korea ; Mongoloid Race*

OBJECTIVE: Behcet? disease (BD) is a chronic inflammatory disorder affecting several organs. The etiology of BD remains unclear, although genetic factors, infectious agents, and immune mechanisms have been studied. The association of BD with certain genetic factors, especially HLA-B51 antigen, is well known in some geographical areas. Nevertheless, the familial occurrence of BD is rare. In this paper, HLA phenotype was evaluated in one family member showing the clustering of BD. METHODS: The serological tissue typing of HLA class I and class II antigens was performed by standard National Institutes of Health microlymphocytotoxicity method in seven family members in which four siblings were affected by BD. The diagnosis of BD was established by the criteria of the International Study Group of BD in these four siblings. RESULTS: In this family study, all members had HLA-A2 and DQ3 antigens. Although HLA-B51 antigen was positive in six out of seven family members, BD was developed in three of the six having HLA-B51 antigen. Three siblings had the exact same HLA phenotype. However, only one person had BD among three siblings with identical HLA phenotype. In addition, all siblings who developed erythema nodosum-like lesion had HLA-B51 antigen. CONCLUSION: This family suggests that the familial clustering of BD may not be explained solely by a susceptible HLA phenotype. The environmental factor or other genetic factors besides HLA-B51 might play a role in the development of BD. Furthermore, more studies and information will be needed to clarify the role of A2 and DQ3 antigens in BD.
Diagnosis ; Erythema ; Histocompatibility Antigens Class II ; Histocompatibility Testing ; HLA Antigens* ; HLA-A2 Antigen ; HLA-B51 Antigen ; Humans ; National Institutes of Health (U.S.) ; Phenotype ; Siblings

OBJECTIVETo analyze the status of HLA-DPA1 and DPB1 matching for unrelated donor-recipient pairs matched at high-resolution allele level for HLA-A, B, C, DRB1 and DQB1 loci.

METHODSA total of 76 unrelated donor-recipient pairs matching at allele level for HLA-A, B, C, DRB1 and DQB1 loci were subjected to HLA-DPA1 and DPB1 sequence-based typing (SBT). HLA-DPA1and DPB1 matching status at high-resolution allelic level was also analyzed.

RESULTSThe allelic identity ratio for single HLA-DPA1 and DPB1 were 17.1% and 9.2%, respectively. HLA-DPA1 and DPB1 allelic identity ratio were both very low. The majority of unrelated donor-recipient pairs (73.7%) had an incompatibility at 1 HLA-DPA1 allele, 9.2% of pairs had an incompatibility at 2 DPA1 alleles. As for the high-polymorphic HLA-DPB1 gene, 57.9% of studied donor-recipient pairs had an incompatibility at 1 HLA-DPB1 allele, almost 1/3 (32.9%) of them were completely incompatible. When HLA-DPA1 and DPB1 genes were analyzed together, the donor-recipient pairs matched at 2/4 was the most common (51.4%), 4/4 allelic complete matched pairs accounted for 5.6%, and 0/4 matched pairs accounted for 8.3%.

CONCLUSIONOur results indicated that the ratio of HLA-DPA1 and DPB1 complete match in the unrelated donor-recipient pairs matching at allelic level for HLA-A, B, C, DRB1 and DQB1 loci were very low. The effect of HLA-DPA1 and DPB1 matching status on clinical unrelated stem cell transplantation still needs to be elucidated.

Alleles ; HLA-DP alpha-Chains ; genetics ; HLA-DP beta-Chains ; genetics ; HLA-DQ beta-Chains ; genetics ; Histocompatibility Antigens Class I ; genetics ; Histocompatibility Testing ; methods ; Humans ; Transplantation ; methods ; Unrelated Donors

PURPOSE: The antibody monitoring system (AMS, GTI Inc.) is a solid phase ELISA crossmatch test for the detection of IgG antibody to the donor-specific solubilized HLA class I and class II antigens. The objective of this study was to compare the results of AMS assay with donor specific anti-HLA IgG antibodies (DS-HLA Abs), as determined by ELISA-PRA and flowcytometric crossmatch test (FCXM). METHODS: A total of 132 sera were tested for the presence of DS-HLA Abs by ELISA-EIA, FCXM and AMS assay. RESULTS: DS-HLA Abs were determined in 41 serum samples by an ELISA-PRA panel and FCXM. There was a significant degree of concordance (84.8%) between the results from the FCXM and AMS (P<0.001). The sensitivity, specificity, the positive predictive value and the negative predictive value of AMS assay to detect DS-HLA Abs was 90.2%, 93.4%, 86.0%, 95.5%, respectively. The AMS is a simple, objective test and it has several advantages over the cell-based crossmatch test such as elimination of non-HLA antibody reactivity, elimination of the non-donor specific antibody reactivity, no need for viable cells, and the donor's HLA antigens can be prepared in advance. CONCLUSION: This study suggests that AMS may be useful as a supportive crossmatch test or as a monitoring test after transplantation for detecting class I and/or class II DS-HLA Abs.
Antibodies* ; Enzyme-Linked Immunosorbent Assay ; Histocompatibility Antigens Class II ; HLA Antigens ; Humans ; Immunoglobulin G ; Sensitivity and Specificity ; Tissue Donors* ; Transplantation

BACKGROUND: The association of de novo donor-specific anti-human leukocyte antigens (HLA) antibodies (DSA) and development of antibody-mediated rejection (AMR) in kidney transplant recipients (KTRs) is still undetermined. METHODS: We prospectively screened de novo DSA in 167 KTRs during 32 months after kidney transplantation (KT). Timing of DSA detection was at 3, 6, and 12 months post-transplant and annually thereafter and when clinically indicated. DSA levels were determined by Luminex assays and expressed as mean fluorescence intensity (MFI). We evaluated the incidence, characteristics of DSA, and association between DSA and tacrolimus trough levels or AMR. RESULTS: De novo DSA developed in 16 KTRs (9.6%) and acute AMR occurred more commonly in KTRs with de novo DSA compared to KTRs without de novo DSA (18.8% vs. 0%, P < 0.001). All de novo DSA were against class II antigens. The mean number of DSA was 1.8 ± 1.2 and the average MFI of DSA was 7,399 ± 5,470. Tacrolimus trough level during the first 0–2 months after KT was an independent predictor of DSA development (hazard ratio, 0.70; 95% confidence interval, 0.50–0.99; P = 0.043). No differences were found in the number of DSA, average MFI of DSA, and tacrolimus levels during the first year between de novo DSA-positive KTRs with AMR and those without AMR. CONCLUSION: The results of our study suggest that monitoring of DSA and maintaining proper tacrolimus levels are essential to prevent AMR during the initial period after KT.
Antibodies* ; Fluorescence ; Graft Rejection ; Histocompatibility Antigens Class II ; HLA Antigens ; Incidence ; Kidney Transplantation* ; Kidney* ; Prospective Studies ; Tacrolimus ; Transplant Recipients

BACKGROUND: To monitor the performance of histocompatibility testing laboratories, HLA proficiency survey in Korea has been conducted biannually since 1996. In this report, we summarized the results of the surveys performed in recent two years (2005-2006). METHODS: A total of four proficiency surveys were performed, in which 59-61 laboratories participated. Each survey included three tests for HLA class I (serology and DNA) and class II (DNA) typing and six tests for HLA crossmatch. RESULTS: The overall concordance of serologic typing was 98.9% (355/359) for HLA-A, 97.5% (350/ 359) for HLA-B, and 94.7% (337/356) for HLA-C. The antigens assigned correctly by less than 95% of the participating laboratories were A26 (93.8%), B38 (94.2%), Cw3/Cw10 (90.9%), Cw6 (94.4%), and Cw8 (74.3%). The overall concordance rates of DNA typing were 99.6% (533/535) for HLA-A, 99.8% (539/540) for HLA-B, and 100% (392/392) for HLA-C. Correct assignment of HLA-DRB1 and -DQB1 was reported by 99.2% (98.1-100%) and 96.7% (88.9-100%) for the generic level and 100% and 95.8% (75-100%) for the allelic level, respectively. On the average 3.8% (0-7.7%) of the total laboratories showed unacceptable results in the crossmatch tests. CONCLUSIONS: The rates of correct antigen identification and of unacceptable crossmatch were similar to those of previous surveys, which were considered satisfactory. The Korean proficiency survey program may have contributed to a high quality of HLA tests today and should be continued for further improvements of the tests tomorrow.
Alleles ; Data Collection ; HLA Antigens/*blood/genetics ; HLA-A Antigens/blood/genetics ; HLA-B Antigens/blood/genetics ; HLA-C Antigens/blood/genetics ; HLA-DQ Antigens/blood/genetics ; HLA-DR Antigens/blood/genetics ; Haplotypes ; Histocompatibility Testing/*standards ; Humans ; Korea ; Laboratories ; Quality Control

OBJECTIVEThe purpose of this study was to observe the association between chronic glomerulonephritis (CGN) and human leukocyte antigen (HLA) on DNA level in order to identify susceptible and protective genes and to further explain the possible pathogenesis of CGN.

METHODS1073 renal transplantation patients with Han ethnicity were included in this study. All patients were recruited from three provincial Hospitals during the past ten years. The control group contained 7418 healthy Han volunteer donors from Shandong Hematopoietic Stem Cell Data Bank of China. We collected data about the polymorphism of HLA-I , II and DRB1. Gene frequency (GF), relative risk (RR) and correlation test were analyzed using statistical software. Some patients carrying the susceptible genes were followed up for 1,3 and 5 years, and compared their survival rate respectively.

RESULTSThe frequency of HLA-A23, A25,B15, B40, B53 and DRB1 * 18 alleles increased significantly in CGN patients than in controls, showing that they might be the suspicious susceptibility genes of CGN. After the follow-up periods, the prognosis of patients with the susceptible genes was worse than the controls. The frequency of haplotypes of A23-B44-DRB1 * 18, A25-B15-DRB1 * 07, A3-B70-DRB1 * 11, A68-B13-DRB1 * 04, A11-B10-DRB1 * 12 increased significantly in CGN patients than in controls. There were 8 lower frequencies alleles (including A20, A22, A35, A36, A38, B21, B73 and B78) in CGN patients that were not found in the control group. The frequencies of the HLA-A32, A33, B50, B58, B60, B71, DRB1 * 16 alleles decreased significantly in CGN patients than in controls, showing that they might be the protective genes of CGN.

CONCLUSIONOur data showed that there might be corresponding susceptibility and protective genes of CGN in Han population, in Shandong. There was significant association between the five common haplotype and CGN in Shandong population. However, the prognosis of the patients with the susceptibility genes was worse than the controls.

Adolescent ; Adult ; Aged ; Alleles ; Case-Control Studies ; China ; Female ; Gene Frequency ; Glomerulonephritis ; genetics ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Haplotypes ; Histocompatibility Antigens Class I ; genetics ; Histocompatibility Antigens Class II ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Young Adult