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Results for “HLA polymorphism”

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PubMed1995

HLA-G deletion polymorphism and pre-eclampsia/eclampsia.

OBJECTIVE: To investigate a HLA-G deletion polymorphism in pre-eclamptic pedigrees and the general population. DESIGN: A population association study of HLA-G genotypes from pre-eclamptic/eclamptic patients and control groups. SETTING: Analyses undertaken in the School of Biological Sciences, Macquarie University. Patients were from Royal Women's Hospital, Melbourne, and controls were from Westmead Hospital and Macquarie University, Sydney. SUBJECTS: One hundred and ninety-six individuals, consisting of 29 pre-eclamptic/eclamptic (PE/E) patients, 13 individuals born of a PE/E pregnancy, 46 blood relatives of PE/E patients, 21 husbands of PE/E patients, 25 women normotensive in first pregnancy, 15 husbands of women normotensive in first pregnancy and 47 staff and students of Macquarie University. RESULTS: Genotypic and gene frequencies were not significantly different in the seven groups examined. CONCLUSION: There is no detectable relationship between susceptibility to pre-eclampsia or being born of a pre-eclamptic pregnancy and HLA-G genotype.

Eclampsia↗

PubMed1994

Genes within the HLA class II region confer both predisposition and resistance to primary biliary cirrhosis.

Nonradioactive sequence-specific oligonucleotide probes for the polymorphic HLA class II genes have been used to type samples from 51 Caucasian patients with the autoimmune liver disease, primary biliary cirrhosis, and 240 Caucasian controls. Although the allelic distribution at the DPB1 locus showed no significant variation between patients and controls, there was heterogeneity in the distribution of DR-DQ haplotypes where the frequency of the DRB1*0801-DQA1*0401/0601-DQB1*04 haplotype was significantly increased in the patients, suggesting it confers susceptibility to this disease. Two other haplotypes, DRB1*1501-DQA1*0102-DQB1*0602 and DRB1*1302-DQA1*0102-DQB1*0604, were significantly reduced in the patients, suggesting they confer protection. Tests of the individual loci show that resistance to this disease is most strongly associated with the DQA1*0102 allele shared by both protective haplotypes. Due to linkage disequilibrium it is unclear whether multiple genes or a single locus on the susceptible DR8 haplotype are needed for predisposition. These data show that distinct HLA class II alleles confer both predisposition and resistance to PBC and provide insight into the role that these genes may play in the immunopathogenesis of this disease.

Causality↗

PubMed1999

[Polymorphism of HLA-DRB1, DQB1 in the Hans of north China].

OBJECTIVE: To understand polymorphism of HLA-DRB1, DQB1 in the Hans of north China and obtain more comprehensive and accurate data on genetics at DNA level. METHODS: Polymerase chain reaction-sequence specific primers (PCR-SSP) were used to determine HLA-DRB1, DQB1 alleles in 107 unrelated healthy Han individuals of north China. RESULTS: The authors determined 14 DRB1, 9 DQB1 alleles, which included not only the allele frequencies that corresponded to the gene frequencies of DR, DQ loci determined by other 9 cooperating labs but also the allele frequencies of DRB1*15, DRB1*16, DQB1*0301, DQB1*0302, DQB1*0303, DQB1*05, DQB1*0601, DQB1*0602, and DQB1*0604 that other serology labs did not report. CONCLUSION: This study has obtained a more comprehensive and accurate data set of the normal allele frequencies and linkage disequilibrium parameters of HLA-DRB1, DQB1 in the Hans of north China, which may be of significance in the studies on population genetics and disease association.

Alleles↗

PubMed1999

HLA class II polymorphism in cystic fibrosis. A possible modifier of pulmonary phenotype.

Evolution of lung damage is highly variable in cystic fibrosis (CF) even in patients with the same cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The analysis of genetic factors other than CFTR may help our understanding of genotype-phenotype relationships in CF. As human leukocyte antigen (HLA) class II polymorphism has been associated with a number of diseases including autoimmune and inflammatory diseases, asthma, and allergy, we investigated the possibility that HLA polymorphism contributes to CF-associated pulmonary inflammation. Among the 98 adult CF patients tested, the genotypic frequencies of DR4 and DR7 alleles (serologic group DR53) and DR7/ DQA*0201 haplotype were higher than in 39 selected control subjects without atopy (p </= 10(-)6, relative risk [RR] = 22, and p </= 5.10(-)4, RR = 27, respectively) and in a random population. No significant difference of these allelic distributions was found according to the CFTR genotype. In the CF patients, the DR7 allele was significantly associated with an increase in total IgE and with chronic Pseudomonas aeruginosa colonization (100% of DR7 versus 83% of non-DR7 patients being colonized, p < 0.05). Our results suggest that genetic factors known to modulate the immune response might contribute to chronic infection with Pseudomonas, increased total IgE, and pulmonary outcome in CF.

Adult↗

PubMed1990

Diagnostic, prognostic and therapeutic aspects of systemic lupus erythematosus and rheumatoid arthritis.

Rheumatoid arthritis and systemic lupus erythematosus are rheumatic diseases characterized by excessive immunoreactivity. Exaggerated immunity is manifested as auto-antibody production and aberrant cell-mediated reactions directed against autologous tissue. Although the mechanisms and site for abnormal immune responses are not completely understood, risk factors that predispose an individual to develop rheumatoid arthritis or systemic lupus erythematosus can be defined. Genetic factors, especially HLA genes, play an important role in rendering a host susceptible to the sequelae of immunologically mediated diseases. Modern technology, such as T-cell cloning, can be used to dissect polymorphic HLA determinants involved in the genetic susceptibility for rheumatoid arthritis and systemic lupus erythematosus. Mapping of disease-associated determinants in rheumatoid arthritis patients suggests that polymorphic sites within the third hypervariable region of the HLA-DR beta 1-chain are functionally involved in the initiation and perpetuation of the disease. These HLA-determinants function to mediate the contact between the HLA- and the T-cell receptor molecules. In systemic lupus erythematosus patients, the role of disease associated molecules appears to be distinct; genetic susceptibility is correlated to patterns of auto-antibody productions. Immunogenetic studies may provide diagnostic tools to subset patients with rheumatoid arthritis and systemic lupus erythematosus and develop prognostic markers to tailor immunomodulatory therapy. Both diseases are characterized by high levels of morbidity and mortality, but can now be mitigated by the careful and judicious use of immunosuppressives.

Arthritis, Rheumatoid↗

PubMed1982

The role of the human major histocompatibility complex in cytotoxic T-cell responses to virus-infected cells.

The human major histocompatibility complex (HLA) has been demonstrated to play two roles in the generation and expression of cytotoxic T-lymphocyte responses to virus-infected cells: (1) cytotoxic T cells can only recognize viral antigens in conjunction with antigens encoded by HLA-A and -B genes; and (2) HLA-linked genes may control the capacity to generate T-cell responses to a given virus or to virus in conjunction with particular self HLA-A and -B antigens. Analysis of T-cell responses generated in vivo to Epstein-Barr virus suggests that human T cells may recognize virus in conjunction with antigens other than the class I HLA polymorphic specificities.

Chromosome Mapping↗

PubMed1990

HLA class I homologous transcripts in the human embryonal carcinoma cell line Tera-2.

We have used the human teratocarcinoma-derived embryonal carcinoma cell line Tera-2 cl. 13 to explore the putative expression of novel HLA class I(-like) genes. Serological analyses revealed that Tera-2 cells do not express polymorphic HLA class I (-A, -B, -C) specificities, but do express HLA class I-like antigens. These phenotypic properties parallel those of certain mouse embryonal carcinoma cells. To study the expression of HLA class I(-like) genes in the Tera-2 cells two different approaches were used. Screening of a Tera-2 cDNA library with a full-length HLA class I cDNA probe under conditions that would allow for the identification of relatively distinct HLA class I-like sequences yielded 27 positive clones, all of which were of the regular HLA-A, -B, -C type. Reverse northern hybridizations of the restriction enzyme-digested Tlab region comprising cosmids with Tera-2 cDNA as the probe resulted in the identification of several putative human genes whose equivalents map within the mouse Tla region. However, none of these genes appeared to be structurally related to HLA class I. A putative H3.3 histone gene was identified in the proximal Tla region of the C57BL/10 mouse. It is concluded that no structural homologues of mouse Qa/Tla genes are expressed in the human developmental cell line Tera-2.

Animals↗

PubMed1994

A novel HLA-A*8001 allele identified in an African-American population.

HLA polymorphism varies among different racial origins. Certain antigens are restricted to a particular ethnic group, suggesting that genetic events might have generated further unique polymorphism following racial diversification. In this study, we have identified and characterized a novel HLA-A allele, officially designated A*8001. The class I molecule, HLA-AXBG, encoded by this allele could not be defined by commonly available HLA antisera. We have identified two alloantisera that appear to be monospecific for this new antigen. The observed frequency of AXBG antigen specificity is 2% in African Americans among the total of 254 tested, but it has not been found in 305 Caucasians tested. IEF and cDNA sequencing analyses on multiple individuals revealed that AXBG antigen defined by the two antisera are encoded by an identical HLA-A*8001 allele and it has a number of unique amino acid residues that have not been observed among other HLA-A alleles but are known to occur in certain human nonclassic class I genes and nonhuman primate class I genes. The ability to identify the new HLA-AXBG antigen will improve the precision of HLA-A typing in black populations and enable us to match a patient with a donor for this otherwise undefined antigen in transplantation.

Alleles↗

PubMed1992

[Automated measurement of cell destruction with the Patimed System in comparison with conventional HLA typing].

HLA molecules serve as identity markers for immunocompetent cells which respond to pathogens and transplant tissue antigens to distinguish self from non-self. The continuous discovery of new HLA polymorphisms which are associated with various diseases or are involved in graft rejection continuously increases the number of HLA antigens which need to be identified for each individual. We defined the HLA class I and HLA class II antigens with the NIH standard microcytotoxicity system and compared the results with those obtained using the commercially available automated Patimed system. Our results show that serological identification of HLA antigens with the Patimed system is reliable. It can be recommended for routine as well as for research purposes.

B-Lymphocytes↗

PubMed2002

[The relationship between silicosis and the polymorphism of HLA-DRB1 , DQB1 genes].

OBJECTIVE: To investigate the relation between the susceptibility to silicosis and the polymorphism of HLA-DRB1 *, DQB1 * genes in Chinese Hans. METHODS: HLA-DRB1 * and DQB1 * gene polymorphism were tested in 48 silicosis patients and 100 normal controls by using polymerase chain reaction of sequence-specific primers (PCR-SSP). RESULTS: The allele frequencies of DRB1 * 1401 and DQB1 * 05 in silicosis patients were significantly higher than those in normal controls (chi 2 = 5.61, P = 0.0066, RR = 17.40; chi 2 = 10.70, P = 0.0011, RR = 3.81, respectively), while the allele frequency of DRB1 * 09 was significantly lower in silicosis patients than that in controls (chi 2 = 5.70, P = 0.0187, RR = 0.21). There was a significant difference between the patient group and control group. CONCLUSION: HLA-DRB1 * 1401 and DQB1 * 05 may be the susceptible genes and HLA-DRB1 * 09 the protection gene of silicosis, both susceptibility and protection may be related to HLA-DR gene locus. The joint action of allele genes may affect the pathogenesis of silicosis.

Gene Frequency↗

PubMed1983

Monoclonal antibody against HLA-Aw32 + A25. Is HLA-Aw32 an allele with no unique antigenic determinant?

In the present paper we describe the production and characterization of a monoclonal antibody (Mab) recognizing HLA-Aw32 + A25 antigens. NS1 murine myeloma cells were fused with splenocytes from a BALB/c mouse immunized with normal human peripheral blood (PB) lymphocytes of phenotype A1, Aw32; B7,B37,Cw-,Cw-;DR2,DRw10. Supernatants were first screened against Cr51-labeled immunizing cells by complement dependent cytotoxicity 51Cr-CDC). Cultures identified as producing cytotoxic antibodies were subcultured and the supernatants tested against a selected panel of HLA typed cells by the NIH microcytotoxicity method. One culture producing antibody reacting with an HLA polymorphism was detected. This hybrid, designated CATA 1, was cloned twice by limiting dilution and obtained in ascitic form. Specificity of CATA 1 Mab was evaluated against a panel of 120 PB T cells from normal donors. CATA 1 reacted with cells bearing HLA-A25 or HLA-Aw32 antigens. In addition, a reaction was observed with a cell of phenotype A2,Aw31; B17,Bw49. Isoelectric focusing revealed the monoclonal nature of CATA 1, with immunofixation identifying it as an IgG molecule. Absorption studies have demonstrated that CATA 1 recognizes a common determinant on HLA-A25 and HLA-Aw32. The finding that this Mab recognizes the same CREG as alloantisera against HLA-Aw32 suggests that this antigen has no unique epitopes.

Alleles↗

PubMed2005

[Relationship between pneumoconiosis and the polymorphisms of HLA-DRB1, DQB1 genes].

OBJECTIVE: To explore the relationship between the polymorphism of HLA-DRB1*, DQB* genes and the susceptibility of pneumoconiosis. METHODS: 1:1 case-control study was adopted. one hundred and thirteen cases of I grade pneumoconiosis were investigated. The control group were workers exposed to dust, who were the same sex, nationality, work place, time of beginning exposure and the cumulative exposure ages not over 2 years. PCR-SSP was used to detect 9 alleles in HLA-DRB1*, DQB1*. Information on related factors of pneumoconiosis was collected using a questionnaire. Univariate and multivariate logistic regression analysis were carried out with 1:1 case-control methodology. RESULTS: The frequency of HLA-DRB1*08 allele in case group was significantly higher than that of the controls (OR: 6.000; 95% CI: 1.9060 - 18.9414). The frequencies of HLA-DRB1*09, HLA-DQB1*06 in case group were significantly lower than those of the controls (OR: 0.259, 0.300; 95% CI: 0.1436 - 0.6268, 0.1149 - 0.5837 respectively). There were significant relationship between HLA-DRB1*08, HLA-DRB1*09, HLA-DQB1*06 alleles and pneumoconiosis after adjusting age, smoking, beginning age of exposure and cumulative length of exposure with multivariate logistic regression analysis (OR: 7.804, 0.225, and 0.269; 95% CI: 2.077 - 29.307, 0.083 - 0.609 and 0.117 - 0.613 respectively. Survival analysis showed that HLA-DQB1*06 allele was a protective factor and HLA-DRB1*08 allele was a risk factor for affecting pneumoconiosis latent period. CONCLUSION: HLA-DRB1*08 allele may be the susceptible risk gene for pneumoconiosis. HLA-DQB1*06 may be the protective gene against developing pneumoconiosis.

Adult↗

PubMed2002

MHC susceptibility genes to IgA deficiency are located in different regions on different HLA haplotypes.

Familial predisposition to IgA deficiency (IgAD) suggests that genetic factors influence susceptibility. Most studies support a polygenic inheritance with a susceptibility locus (designated IGAD1) in the MHC, but its exact location is still controversial. This study aimed to map the predisposing IGAD1 locus (or loci) within the MHC by investigating the pattern of association of the disease with several markers in the region. DNA-based techniques were used to type individual alleles of four polymorphic HLA genes (HLA-DR, -DQA1, -DQB1, and HLA-B), six microsatellites (all located between HLA-DR and HLA-B), and three single nucleotide polymorphisms on the TNF gene. The frequencies of these alleles were compared among ethnically matched populations comprising 182 patients and 343 controls. Additionally, we investigated parents and siblings of 100 of these patients. All four parental haplotypes were established in each family (n = 400), and transmission disequilibrium tests were performed. Surprisingly, our results did not support the hypothesis of a unique susceptibility gene being shared by all MHC susceptibility haplotypes. On HLA-DR1 and -DR7-positive haplotypes IGAD1 mapped to the class II region, whereas on haplotypes carrying HLA-DR3 the susceptibility locus mapped to the telomeric end of the class III region, as reported previously. Our results show how, in complex diseases, individuals may be affected for different genetic reasons and a single linkage signal to a region of a chromosome may actually be the result of disease-predisposing alleles in different linked genes in different pedigrees.

Alleles↗

PubMed2005

[Polymorphism of HLA-A,-B and DRB1 in Han population of Shanxi province].

OBJECTIVE: To investigate the polymorphism of HLA-A, -B, -DRB1 genes in Han population in Shanxi of China. METHODS: Polymerase chain reaction-sequence specific primers (PCR-SSP) technique was used to identify the polymorphism of HLA-A, -B, -DRB1 genes of 7440 healthy and unrelated individuals of Han population in Shanxi, and the gene frequency distribution of HLA-A, -B, -DRB1 genes in population was compared with the results from other populations. RESULTS: Eighteen HLA-A, forty HLA-B and thirteen HLA-DRB1 alleles were found. The frequencies of A*02, A*24, A*11, A*01, A*03, B*13, B*51, B*15, B*40, B*35, DRB1*15, DR*09, DR*12, DR*04, DR*07 alleles in Hans of Shanxi were significantly higher and displayed distinctive distribution profiles when compared with those of Caucasian and Afro-American. CONCLUSION: The HLA-A,-B,-DRB1 distribution in Shanxi Han population shares some genetic characteristics with other Han populations in northern part of China, but it exhibits its own characteristics.

Adolescent↗

PubMed1988

Combined treatment with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha up-regulates the expression of HLA class I determinants in Burkitt lymphoma lines.

Cell lines derived from Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt lymphoma (BL) have a low or defective expression of polymorphic HLA class I determinants compared to EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin and are resistant to lysis by cytotoxic T lymphocytes (CTL) specific for the corresponding determinants (M. G. Masucci, S. Torsteinsdottir, J. Colombani, C. Brautbar, E. Klein, and G. Klein, Proc. Natl. Acad. Sci. USA 84, 4567, 1987; S. Torsteinsdottir, C. Brautbar, E. Klein, G. Klein, and M. G. Masucci, Int. J. Cancer, 41, 913, 1988). In order to investigate whether this phenotypic trait of the tumor cells can be modulated by agents known to enhance HLA class I antigen expression, pairs of LCL and BL lines were cultured in the presence of recombinant human interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Three low HLA A11 expressor EBV-negative BL lines, DG 75, BL 28, and BL 41, reacted significantly stronger with the anti-HLA A11 monoclonal antibody (Mab) AUF 5.13 after combined treatment with 500 U/ml IFN-gamma and 500 U/ml TNF-alpha. Reactivity with the AUF 5.13 and with other anti-polymorphic class I Mab's was up-regulated also in in vitro EBV-converted sublines of BL 28 and BL 41. The increment of antigen expression depended on the baseline expression in untreated cells. It was largest for the low expressor lines and decreased proportionally to the level of up-regulation induced by EBV conversion. Up-regulation of HLA A11 was accompanied by induction of sensitivity to HLA A11-specific CTLs in BL 28 and its converted subline E95A BL28 while BL 41 and E95A BL 41 remained resistant. The treatment did not affect significantly HLA A11 expression of two EBV-carrying, low HLA A11 expressor BL lines, WW-1-BL and WW-2-BL, and of the EBV-carrying BL 72 line that had a high spontaneous expression. The results suggest that the down-regulation of class I antigen expression is reversible in some but not all BL lines.

Antibodies, Monoclonal↗

PubMed1998

A reliable and efficient high resolution typing method for HLA-C using sequence-based typing.

Serological typing of HLA-C has been poor and almost half of its alleles are serologically undetectable blanks in most populations. Therefore, DNA typing techniques have been used to identify and type for the HLA-C gene. Sequence-based typing (SBT) has proven a major typing strategy for highly polymorphic HLA genes. The technique enables direct identification of all sequence motifs without the need to continuously adjust primers. Here we describe a reliable solid-phase SBT strategy for HLA-C which can be used to distinguish all currently known HLA-C alleles without prior knowledge gained by low resolution typing. Exons 2 and 3 were amplified and sequenced and if necessary sequences of exons 1 and 5 were determined. A total of 257 individuals were typed for HLA-C using this protocol and 30 of the 42 known HLA-C alleles were detected. All heterozygous combinations found in this study were unambiguously discriminated. One hundred and forty-four individuals from the Dutch population were typed randomly. In this group Cw*0701 and *0702 were the most frequently detected alleles. Of the serological Cw blank alleles Cw*1203 was found to have the highest frequency (16%). From the total group 212 individuals were typed serologically and 106 were retyped with 97 selected antisera to further compare serological and molecular defined phenotypes. Discrepancies between serological typing and SBT are mainly attributable to the serologically Cw blank alleles Cw*12-18. The high resolution SBT protocol described will be a valuable tool for the identification of HLA-C alleles and the determination of the role of HLA-C in marrow and organ transplantation.

Alleles↗

PubMed2000

Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in Northern Sweden.

HLA genes have been shown to be associated with cervical intraepithelial neoplasia (CIN), a precursor of cervical cancer. The human papillomaviruses (HPV) types 16 and 18 are the major environmental cause of this disease. Because the immune system plays an important role in the control of HPV infection, the association of polymorphic HLA could lead to a different immune response to control the development of cervical cancer. The aim of this study was to analyze the association between CIN and a microsatellite polymorphism of tumor necrosis factor (TNFa) taking HPV exposure and CIN-associated HLA haplotypes into account. In a nested case-control study in northern Sweden, 64 patients and 147 controls matched for age and sex and derived from the same population-based cohort were typed for TNFA, HLA-DR, and DQ and assayed for antibodies to HPV types 16 and 18. TNFa polymorphism was not associated with CIN per se. However, there was a significant increase in the frequency of TNFa-11 among HPV16-positive and HLA DR15-DQ6 (B*0602) patients compared with HPV16- and HLA-DQ6-negative patients (odds ratios, 5.4 and 9.3, respectively). The relative risk for CIN conferred by the combination of TNFa-11, HLA-DQ6, and HPV 16 positivity was 15. Our study suggests that the TNFa-11 allele is associated with HPV16 infection and associated with CIN in combination with HLA-DQ6 but not by itself.

Adult↗

PubMed2002

[Tumor necrosis factor alpha HLA-DRB(1) gene polymorphism and genetic susceptibility to cirrhosis].

OBJECTIVE: To study the relationship between the gene polymorphism of HLA-DRB(1) and tumor necrosis factor (TNF)alpha with the genetic susceptibility to cirrhosis. METHODS: The gene polymorphism of DRB(1) and TNF alpha of 106 cases of cirrhosis due to HBV and 108 controls were detected by means of polymerase chain reaction-sequence specific primer and RFLP techniques. RESULTS: The frequency of DRB(1) * 120X and TNF2/1 was increased in the patients as compared with the controls (35.9% vs 11.1%, P < 0.001, 19.8% vs 10.2%, P < 0.05 respectively), The frequency of DRB(1) * 150X allele was reduced in the patients as compared with the controls (13.2% vs 30.6%, P < 0.05). It is suggested that the gene polymorphism of HLA-DRB(1) and TNF alpha to be associated with genetic susceptibility to cirrhosis. Cross analysis showed that DRB(1) * 120X allele was more strongly associated with genetic susceptibility to cirrhosis than TNF2 allele. CONCLUSIONS: The genetic susceptibility to cirrhosis is associated with DRB(1) * 120X and TNF2 allele, persons with DRB(1) * 120X and TNF2 allele have an increased risk for the liver cirrhosis occurrence; DRB(1) * 120X allele may be a susceptibility gene to liver cirrhosis and DRB(1) * 150X allele may be a protective gene from liver cirrhosis.

Disease Susceptibility↗