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 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

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

OBJECTIVETo delineate the immune regulatory pathway of benzene poisoning by using gene expression profile analysis.

METHODSPeripheral white blood cell gene expression profile of 7 benzene poisoning patients, including one aplastic anemia, was determined by microarray. Seven chips from normal workers were served as controls. Cluster analysis of gene expression profile was performed. Differentially expressed immune genes associated with benzene poisoning were determined.

RESULTSAmong the 2 779 target genes, 38 genes differentially expressed were identified, including 10 up-regulated genes such as CD59, TRA@, MCP etc, and 14 down-regulated genes such as HLA-DMB, HLA-DQA1, HLA-DPB1, ITGB2, PFC etc. Cluster analysis showed that the expression profiles of 38 genes were associated with benzene poisoning.

CONCLUSIONDifferentially expressed immune genes may play an important role in the pathogenesis of benzene poisoning.

Benzene ; poisoning ; CD59 Antigens ; genetics ; Case-Control Studies ; Cluster Analysis ; Female ; Gene Expression Profiling ; HLA-D Antigens ; genetics ; HLA-DP beta-Chains ; genetics ; HLA-DQ alpha-Chains ; genetics ; Humans ; Oligonucleotide Array Sequence Analysis

BACKGROUND: The umbilical cord blood (UCB) is highlighted to be a alternative source of hematopoietic stem cells with a hope of resolving major problems of bone marrow transplantation, which are the lack of suitable HLA-matched donors and the occurrence of graft-versus-host disease (GVHD). In this study we have assessed the immunological potential of lymphocytes in UCB, which could mediate GVDH, by immunophenotypes and functional assays on 20 UCB and 19 adult peripheral blood as controls. METHODS: Immunophenotyping of lymphocytes were performed by one and two color flow cytometry (FACSort, Becton Dickinson, USA) using monoclonal antibodies (CD3, CD4, CD8, CD19, CD16/56, CD45RA, CD45RO, HLA-DR, HLA-DQ, HLA-DP, TCRalphabeta, TCRgammadelta). To assess proliferative responses, UCB lymphocytes were cultured in the presence of phytohemagglutinin (PHA) (5, 20, 100 ug/mL) and concanavalin A (ConA) (1, 5, 10 ug/mL). After 72 hour culture and 3H-thymidine pulsing, specific 3H-thymidine uptake was compared to control cells (without mitogen) by stimulation index (SI). RESULTS: In phenotypic analyses, the percentages of CD4, CD8, CD45RO, TCRgammadelta and HLA- DP positive cells were significantly lower in UCB compared with the adult controls, while the percentage of CD45RA positive cells was increased in UCB. In addition, the percentages of B cell (CD19), NK cell (CD16/56), HLA-DR, HLA-DQ and TCRalphabeta were comparable to those in adult controls. In mitogen stimulated culture, UCB lymphocytes showed a significant lower proliferative responses at 20, 100 ug/mL of PHA, and 5, 10 ug/mL of ConA concentrations. CONCLUSIONS: We have observed that UCB lymphocytes appeared to be phenotypically and functionally immature. Thus, UCB might be a attractive source for hematopoietic stem cells in that these UCB cells may have lower immunological potentials mediating GVHD after transplantation.
Adult ; Antibodies, Monoclonal ; Bone Marrow Transplantation ; Concanavalin A ; Fetal Blood* ; Flow Cytometry ; Graft vs Host Disease ; Hematopoietic Stem Cells ; HLA-DP Antigens ; HLA-DQ Antigens ; HLA-DR Antigens ; Hope ; Humans ; Immunophenotyping ; Killer Cells, Natural ; Lymphocytes* ; Negotiating ; Tissue Donors ; Transplantation ; Umbilical Cord*

BACKGROUNDKeshan disease (KD) is an endemic cardiomyopathy in China. The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease. Young women of child-bearing age are the most frequent victims in rural areas. The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers.

METHODSWe extracted RNA from the peripheral blood mononuclear cells of KD patients (12 women and 4 men) and controls (12 women and 4 men). Then the isolated RNA was amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Gene expression was examined using oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was also performed to validate our microarray results.

RESULTSAmong the genes differentially expressed in female KD patients we identified: HLA-DOA, HLA-DRA, and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7, involved in cardiomyocyte differentiation defect; and ADAMTS 8, CCL23, and TNFSF15, implicated in anti-angiogenic activities. These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD.

CONCLUSIONOur results might help to explain the higher susceptibility of women to this disease.

ADAM Proteins ; genetics ; ADAMTS Proteins ; Adult ; Autoimmunity ; genetics ; physiology ; Bone Morphogenetic Protein 5 ; genetics ; Bone Morphogenetic Protein 7 ; genetics ; Cardiomyopathies ; genetics ; pathology ; Cell Differentiation ; genetics ; physiology ; Chemokines, CC ; genetics ; Enterovirus Infections ; genetics ; pathology ; Female ; Gene Expression Profiling ; HLA-D Antigens ; genetics ; HLA-DQ alpha-Chains ; genetics ; HLA-DR alpha-Chains ; genetics ; Humans ; Male ; Middle Aged ; Myocytes, Cardiac ; cytology ; metabolism ; Oligonucleotide Array Sequence Analysis ; Sex Factors ; Tumor Necrosis Factor Ligand Superfamily Member 15 ; genetics

This study investigated the feasibility of using an hammerhead ribozyme against C II TA, a major regulator of MHC II antigens, to repress the expression of MHC II molecules on Hela cells. A hammerhead ribozyme (Rz464) specific to 463-465 GUC triplet of C II TA and its target gene were transcribed, then mixed up and incubated in vitro. The cleavage products were analyzed by PAGE and silver-staining. Rz464 was then inserted into the pIRES2-EGFP vector (pRz464). Stable transfectants of Hela with pRz464 were tested for class II MHC induction by recombinant human interferon-gamma (IFN-gamma). mRNA of C II TA was measured by RT-PCR. Our results showed that Rz464 could exclusively cleave C II TA RNA. When induced with IFN-gamma, the expression of HLA-DR, -DP, -DQ on pRz464+ Hela was induced, and the mRNA content of C II TA decreased too. It is concluded that Rz464 could inhibit C II TA and thus the family of genes was regulated by C II TA:MHC II molecules. These results provided insight into the future application of Rz464 as a new nucleic acid drug against auto-immune diseases.
Autoimmune Diseases ; therapy ; Base Sequence ; Genetic Therapy ; HLA-DP Antigens ; metabolism ; HLA-DQ Antigens ; metabolism ; HLA-DR Antigens ; metabolism ; HeLa Cells ; Humans ; Interferon-gamma ; pharmacology ; Molecular Sequence Data ; Nuclear Proteins ; immunology ; RNA, Catalytic ; genetics ; metabolism ; pharmacology ; physiology ; Recombinant Proteins ; Reverse Transcriptase Polymerase Chain Reaction ; Trans-Activators ; antagonists & inhibitors ; genetics ; immunology ; Transfection

OBJECTIVETo investigate the association between the polymorphism of human leucocyte antigen (HLA)-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B.

METHODSHLA-DRB1, -DQA1 and -DQB1 alleles in 52 patients with chronic hepatitis B, 30 patients with acute hepatitis B and 106 normal control subjects were analysed, using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique.

RESULTSThe allele frequencies of HLA-DRB1 * 0301, -DQA1 * 0501 and -DQB1 * 0301 in the chronic hepatitis B group (17.31%, 25.96%, 35.58%) were markedly higher than that in the normal control group (5.67%, 13.36%, 18.87%), with statistical significance (chi(2)(1) = 12.3068, P(c1) = 0.0074; chi(2)(2) = 9.2002, P(c2) = 0.0157; chi(2)(3) = 15.5938, P(c3) = 0.0075). The allele frequencies of HLA-DRB1 * 1101/1104 and -DQA1 * 0301 in the chronic hepatitis B group (0.96%, 14.42%) were markedly lower than that in the acute hepatitis B group (13.33%, 30%), with significant correlation between them (chi(2)(1) = 11.9206, P(c1) = 0.0145; chi(2)(2) = 8.7396, P(c2) = 0.0167).

CONCLUSIONHLA-DRB1 * 0301, -DQA1 * 0501 and -DQB1 * 0301 were closely associated with the susceptibility to chronic hepatitis B, while HLA-DRB1 * 1101/1104 and -DQA1 * 0301 closely associated with the resistance to chronic hepatitis B. These findings suggested that host HLA class II gene was an important factor determining the outcome of HBV infection.

Adult ; Alleles ; DNA ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; HLA-DQ Antigens ; genetics ; HLA-DQ alpha-Chains ; HLA-DQ beta-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hepatitis B ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic

OBJECTIVETo make a comparative study of HLA-DQA1 and HLA-DRB1 allele frequencies in the cases of endometriosis and adeonmyosis.

METHODSThe allelic types of HLA-DQA1 and HLA-DRB1 were detected by polymerase chain reaction-sequence specific primers (PCR-SSP) technique in 51 cases of endometriosis, 45 cases of adenomyosis, and 44 normal individuals as the control.

RESULTSThe frequencies of HLA-DQA1*0401(7.8%, 10.0%) were significantly increased in the endometriosis group and the adenomyosis group (Pc=0.03, Pc=0.01), and the frequencies of HLA-DQA1*0301(8.8%, 5.6%) were significantly decreased in these two groups (Pc=0.00, Pc=0.00).There was no significant difference between the frequencies of HLA-DQA1 and HLA-DRB1 of endometriosis and adenomyosis.

CONCLUSIONThe results indicate that HLA-DQA1*0301 and *0401 alleles are associated with both endometriosis and adenomyosis, and there is perhaps common mechanism involved in both endometriosis and adenomyosis based on HLA-DQA1 and HLA-DRB1 allele frequencies.

Asian Continental Ancestry Group ; genetics ; Endometriosis ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; HLA-DQ Antigens ; genetics ; HLA-DQ alpha-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Humans ; Polymerase Chain Reaction ; methods

OBJECTIVETo assess the association of haplotype of HLA-DRB1 and HLA-DQA1 alleles with outcomes of hepatitis B virus infection in Han population of north China.

METHODSTwo hundred and seven chronic hepatitis B (HB) patients, two hundred and twelve chronic asymptomatic hepatitis B virus (HBV) carriers (HBV carrier) and one hundred and forty-eight self-limited HBV infection were investigated for HLA-DRB1 and HLA-DQA1 alleles by sequence specific-polymerase chain reaction (PCR-SSP).

RESULTSThe frequency of DRB1*04-DQA1*0301 haplotype was 10.03% in self-limited HBV infection subjects, significantly higher than that in chronic HB patients (3.66%) (P=0.0005)ûthe frequency of DRB1*15/*16-DQA1*0102 haplotype was 6.80% in self-limited HBV infection subjects, significantly higher than 1.94% in chronic HB patients (P=0.0012) and 1.65% in asymptomatic HBV carriers (P=0.0004)ûwhile the frequency of DRB1*04-DQA1*0302 haplotype was 3.10% in chronic HB patients, higher than that in self-limited HBV infection subjects (0.39%) (P=0.0077).

CONCLUSIONIndividuals with different haplotypes composed of HLA-DRB1 and HLA-DQA1 might have different outcomes of HBV infection.

Adolescent ; Adult ; Alleles ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; HLA-DQ Antigens ; genetics ; HLA-DQ alpha-Chains ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Haplotypes ; Hepatitis B ; genetics ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction