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Results for “HLA polymorphism”

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PubMed1985

Characterization and localization of HLA antigens on hydatidiform mole.

Frozen sections of three specimens of hydatidiform mole were stained with monoclonal antibodies to HLA Class I and Class II antigens by means of an indirect immunoperoxidase technique. Class I (HLA A, B, C) antigens were detected on proliferating extravillous trophoblast and on villous stromal cells but not on quiescent villous trophoblast. Trophoblast Class I antigen was detected with four different antibodies to monomorphic determinants but not with antibodies to the appropriate polymorphic HLA A or B type. Stromal cells were reactive with all Class I antibodies. Class II (HLA DR) antigens were not detected on any molar tissue. The expression of HLA antigens by molar tissue is similar to that of the normal first-trimester human placenta.

Antibodies, Monoclonal↗

PubMedDate not supplied

HLA-DRB1 frequencies of the Comorian population and their genetic affinities with Sub-Saharan African and Indian Oceanian populations.

BACKGROUND: Ethnic-historic sources have considered the Comorian population to be the result of an amalgamation of African, Arabian and Southeast Asian groups. AIM: This study seeks to determine the genetic relationships and contributions from Sub-Saharan Africa and Indian Oceania and to reconstruct past migration events. SUBJECTS AND METHODS: The human leukocyte antigen (HLA) polymorphism of a Comorian population was described and analysed. RESULTS: Genetic distances and multidimensional scaling analyses showed complex patterns of genetic differentiation in the Indian Oceanian area as a result of continuous gene flow occurring within the past approximately 2500 years. Nevertheless, the Comorian genetic pool appears to be a mix of Bantu-speaking and Arab populations as testified to by admixture estimations of almost 50-60% and 27-33%, respectively. CONCLUSION: The Comorian population may represent the eastern limit of the recent and massive eastward Bantu expansion. In contrast to the population from Madagascar (Merina), only a restricted influence of Austronesian populations was found.

Africa South of the Sahara↗

PubMed2001

Peripheral blood cell bulk cultures are not suitable for the analysis of the genetic control of T-cell cytokine function.

Recently evidence has been provided for a genetic control of T-cell dependent cytokine production by HLA-class II. Candidate genes in multiple sclerosis, a T-cell mediated autoimmune disease, are the disease-associated DR2, DQ6, Dw2 haplotype. Previous observations by us and others imply a HLA-DR2 dependent propensity of antigen-specific T-cell lines to produce increased amounts of TNF-alpha/beta. Here, we tested a possible association between HLA or disease status with cytokine production employing the simple and widely used method of bulk cultures. Peripheral blood cells of 48 patients and 68 healthy individuals were analyzed. We observed no significant differences of the cytokine production in relation to disease status or any HLA polymorphism. Our data indicate that, in contrast to monoclonal T-cell cultures, bulk cultures are not suitable to detect immunogenetic control of T-cell function.

Alleles↗

PubMed1997

Evaluation of possible population bias among high-dose atomic bomb survivors in the frequency of the HLA-DQA1 allele and DR antigen types.

Many studies have suggested a relationship between certain alleles of the human leukocyte antigen (HLA) and the prevalence of some diseases or the immunological responsiveness to certain antigens. Furthermore, our studies in the past have demonstrated decreased immune function among atomic-bomb survivors who were exposed to high doses of radiation. However, no studies have addressed the possibility of various degrees of radiation-induced immune suppression being dependent on HLA type. To investigate the possibility of differing frequency distributions of HLA type in the Hiroshima atomic bomb survivors, HLA-DQA1 alleles and HLA-DR antigens were typed for 291 survivors in a high-dose group (>1.5 Gy), 339 survivors in an intermediate-dose group (0.005-1.5 Gy), and 388 in a distally exposed control group (<0.005 Gy). These doses are whole-body exposures, mainly from gamma-rays but with a small neutron component. When examinees were grouped by distinct pairs of HLA-DQA1 allele or HLA-DR antigen, no sex- or dose-related differences were found. However, when subjects were grouped by the presence of a specific allele or antigen, males carrying DQA1*0103 in at least one of their two HLA-DQA1 loci exhibited frequency distributions that decreased as radiation dose increased. These results suggest, although weakly, a possible population bias among male survivors with respect to HLA polymorphism. However, this bias is unlikely to be great enough to have a substantial effect on the cancer risk estimates.

Adolescent↗

PubMed2003

HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma.

AIM: To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei Province. METHODS: HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers(PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with PCR.SAS software was used in statistics. RESULTS: Allele frequency (AF) of HLA-DRB1*0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs 0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1*0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 alleles. CONCLUSION: HLA-DRB1*0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1*0901 may be susceptible to esophageal carcinoma.

Adult↗

PubMed1996

C4 polymorphism and extended HLA haplotypes in Namibian San and Khoi and in South African Xhosa.

We studied C4A and C4B polymorphisms and HLA-B and -DR associations in the San, Khoi and Xhosa. C4A and C4B alleles were determined using conventional protein allotyping methods. The C4A*3, C4B*1 haplotype had a high frequency (30-55%) in all populations. The frequency of C4A*3, C4B*Q0 was 7-19%. The C4A*Q0, C4B*1 haplotype was frequent (15%) in the Khoi but very rare in the San (P < 0.001). C4A*12 A*91, C4B*Q0 was frequent in the Xhosa (15%) but rare in the San and Khoi (P < 0.001). Alleles C4A*5 and C4A*6, and the C4B*2 B*92 duplication were only found in the Xhosa. C4A alleles A*4, A*45, A*58, A*12, A*14, A*19 and the C4A*3 A*91 duplication were only found in the San/Khoi population group. In the San, fourteen extended haplotypes were found in a relatively high frequency (2-7%). In the Xhosa, one extended haplotype (B42, C4A*12 A*91, C4B*Q0, DR18) was found in a very high frequency (13%) and was characteristic for this group; five other extended haplotypes were found with a low frequency (< 3%).

Complement C4a↗

PubMed2004

Human genetics and responses to influenza vaccination: clinical implications.

Influenza A and B viruses are negative-strand RNA viruses that cause regular outbreaks of respiratory disease and substantially impact on morbidity and mortality. Our primary defense against the influenza virus infection is provided by neutralizing antibodies that inhibit the function of the virus surface coat proteins hemagglutinin and neuraminidase. Production of these antibodies by B lymphocytes requires help from CD4+ T cells. The most commonly used vaccines against the influenza virus comprise purified preparations of hemagglutinin and neuraminidase, and are designed to induce a protective neutralizing antibody response. Because of regular antigenic change in these proteins (drift and shift mutation), the vaccines have to be administered on an annual basis. Current defense strategies center on prophylactic vaccination of those individuals who are considered to be most at risk from the serious complications of infection (principally individuals aged >65 years and those with chronic respiratory, cardiac, or metabolic disease). The clinical effectiveness of influenza virus vaccination is dependent on several vaccine-related factors, including the quantity of hemagglutinin within the vaccine, the number of doses administered, and the route of immunization. In addition, the immunocompetence of the recipient, their previous exposure to influenza virus and influenza virus vaccines, and the closeness of the match between the vaccine and circulating influenza virus strains, all influence the serologic response to vaccination.However, even when these vaccines are administered to young fit adults a proportion of individuals do not mount a significant serologic response to the vaccine. It is not clear whether these nonresponding individuals are genetically pre-programmed to be nonresponders or whether failure to respond to the vaccine is a random event. There is good evidence that nonresponsiveness to hepatitis B vaccine, another purified protein vaccine, is at least partially modulated by an individual's human leucocyte antigen (HLA) alleles. Because CD4+ T cells, which control the neutralizing antibody response to influenza virus, recognize antigens in association with HLA class II molecules, we recently conducted a small study to investigate whether there was any association between HLA class II molecules and nonresponsiveness to influenza virus vaccination. This work revealed that the HLA-DRB1*0701 allele was over represented among persons who fail to mount a neutralizing antibody response. This preliminary finding is important because it potentially identifies a group who may not be protected by current vaccination strategies. Further investigation into the role of HLA polymorphisms and nonresponse to influenza virus vaccination, and vaccination against viruses in general, is clearly required.

Age Factors↗

PubMed2002

Novel polymorphisms in HLA-DOA and HLA-DOB in B-cell malignancies.

In B cells, HLA-DO controls HLA-DM-mediated peptide loading on MHC class II molecules. We analyzed whether HLA-DO mutations are associated with autoimmune diseases characterized by an autoantibody component and with a linkage to HLA-DR or HLA-DQ. These diseases include systemic lupus erythematosus, rheumatoid arthritis, celiac disease, and Graves' disease. In addition, several B-cell leukemias were screened for mutations in HLA-DO. A limited number of polymorphisms in DOA and DOB were found, most of which are non-coding changes or result in a conserved amino acid change. A novel non-conserved Arg to Cys mutation in DOA was found in a patient suffering from chronic lymphocytic leukemia. Further analysis did not reveal any effect on the function of HLA-DO. We conclude that HLA-DO variants are not critically involved in the autoimmune diseases and B-cell leukemias studied here.

Autoimmune Diseases↗

PubMed1988

Taq I-generated HLA-DQ alpha polymorphism in Japanese patients with narcolepsy.

Taq I-generated HLA-DQ alpha restriction fragment length polymorphism was examined in Japanese patients with narcolepsy. All patients were DR2 positive and shared a 6.0 kb fragment, although this fragment was found only in 54% of the healthy DR2-positive Japanese. This finding added the DQ alpha gene to the list of candidates for the possible narcolepsy-susceptibility gene. In contrast, there was no complete association between narcolepsy and DX alpha restriction fragment length polymorphism. These findings suggest that a narcolepsy-susceptibility gene is located closer to the DQ locus than to the DX locus.

Chromosomes, Human, Pair 6↗

PubMed1995

Analysis of anti-U1 RNA antibodies in patients with connective tissue disease. Association with HLA and clinical manifestations of disease.

OBJECTIVE: To determine the prevalence of anti-U1 RNA antibodies in connective tissue disease (CTD) patients and evaluate immunogenetic and clinical features of patients possessing these antibodies. METHODS: RNA immunoprecipitation was used to analyze patient and healthy control sera for the presence of anti-R1 RNA antibodies. Enzyme-linked immunosorbent assay and immunoblotting were used to determine small nuclear RNP (snRNP) polypeptide antibodies. HLA polymorphisms were determined by microcytotoxicity and DNA typing. RESULTS: Anti-U1 RNA IgM and IgG antibodies were found in 60% of anti-RNP positive patients. All of the anti-U1 RNA positive patients had anti-70K, and most had anti-A, (U1)snRNP polypeptide antibodies. HLA-DR2/DR4, as well as Raynaud's phenomenon and synovitis, were significantly increased in the anti-U1 RNA positive group. CONCLUSION: The presence of anti-U1 RNA antibodies correlates with anti-70K and anti-A polypeptide antibodies. In addition, the anti-U1 RNA positive CTD patient group is immunogenetically and clinically distinctive from the anti-U1 RNA negative patient group.

Adolescent↗

PubMed2000

HLA-A*6817, identified in the Kolla Amerindians of North-West Argentina possesses a novel nucleotide substitution.

Analysis of HLA polymorphism of the indigenous populations of Central and South America has identified many alleles not seen previously in other populations. We have described a novel allele, B*5113, previously in a Kolla Amerindian individual from North-West Argentina. Here we present a second novel allele from this population: A*6817, which differs from its closest neighbour A*68012 by a single substitution at nucleotide 419. This substitution of adenosine 419 A*68012 for thymidine in A*6817 results in a novel amino acid change (aspartate to valine) at residue 116.

Argentina↗

PubMed1999

Rapid and slow progressors differ by a single MHC class I haplotype in a family of MHC-defined rhesus macaques infected with SIV.

Highly polymorphic HLA class I molecules may influence rates of disease progression of HIV-infected individuals. Recent evidence suggests that individuals who mount vigorous CTL responses to multiple HIV-1 epitopes have reduced viral loads, and survive longer than individuals that make a less robust or less diverse CTL response. It has been difficult, however, to define associations between particular HLA class I alleles and rates of disease progression. This may be due, in part, to the uncontrolled variables associated with naturally acquired HIV infections. Studies using MHC-defined, non-human primates infected with well characterized viral stocks should help to clarify this relationship. To explore the possibility that MHC class I polymorphism can influence disease progression, we infected four Mamu-DRB-identical individuals from a family of MHC-defined rhesus macaques intravenously with 40 TCID50SIVmac239. Two of these macaques developed severe wasting and were euthanized within 80 days of infection, while the other two survived for more than 400 days without showing any symptoms of disease. Since all four of these macaques were Mamu-DRB-identical, we were able to exclude the MHC class II DRB loci as determinant of disease progression. Interestingly, both of the slow progressors made CTL responses to the same three SIV CTL epitopes, which were restricted by two molecules (Mamu-B*03 and B*04) encoded by their common maternal haplotype. The two rapid progressors did not share this haplotype with the slow progressors, and we were unable to detect CTL responses in these two siblings. These observations implicate products of the Mamu-B*03 and B*04 alleles in resistance to disease progression in this family of SIV-infected macaques, and provide additional evidence that certain MHC class I-restricted CTL responses may play a significant role in delaying the onset of AIDS.

Alleles↗

PubMed1996

Strict adherence to a common rank order of T-cell receptor V beta usage in human leucocyte antigen disparate individuals.

In order to investigate the T-cell receptor (TCR) V beta usage in different T-cell subsets, the authors performed flow cytometric analyses using a large panel of TCR V beta-specific monoclonal antibodies on CD4+, CD8+ CD28+ and CD8+ CD28- T cells from 15 random blood donors, six umbilical cords and seven human leucocyte antigen (HLA) identical non-twin sibling pairs. The authors found that the proportion of T cells expressing each V beta gene product was similar within CD4+ and CD8+ CD28+ T cells from all samples studied. For these T-cell subsets a rank order of V beta usage could be identified which was adhered to by all donors. In contrast, within CD8+ CD28- T cells a wide variation of V beta usage was found between individuals, and no rank order correlation could be detected. Members of HLA identical sibling pairs were found to be no more similar in their usage of V beta gene products than pairs of HLA disparate random blood donors. Groups of individuals sharing HLA antigens were no different from the groups not sharing such antigens in their usage of V beta segments. The results suggest that HLA polymorphisms play no more than a minor part in determining TCR V beta usage.

Adult↗

PubMed1985

An immunohistological study of HLA antigen expression by gestational choriocarcinoma.

Two cases of gestational choriocarcinoma have been examined for the expression of HLA and trophoblast antigens using the indirect immunoperoxidase technique on frozen tissue sections. Approximately 40-70% of tumour cells express MHC Class I antigen as detected by a panel of antibodies to monomorphic, or framework, MHC Class I antigenic determinants. Evidence in one case suggests that most of these cells may not express the paternal, polymorphic HLA antigenic determinants but that a small subpopulation do carry the fully antigenically active molecule. These latter may give rise to patient anti-paternal HLA antibodies. Class II (HLA DR or DC) antigens are expressed by none, or very few, tumour cells.

Choriocarcinoma↗

PubMed1980

HLA antigen frequencies in an Irish population.

Two-hundred-and-fifty-three unrelated Irish adults were typed for 24 alleles at the HLA--A and B loci. A high frequency of HLA--B8 (34.8%) was observed compared with results published for other populations. Results of other gene frequencies, haplotype frequencies and linkage disequilibrium values were similar to those of Caucasian population studies. Close similarity of HLA polymorphism distribution was seen in relation to another relatively homogeneous Celtic population from the islands of the Outer Hebrides, off the coast of Scotland.

Alleles↗

PubMed1983

Gm markers in celiac disease.

The association of Ig allotypes with celiac disease was analyzed in a sample of 95 Italian patients typed for HLA polymorphisms. No significant association was found for any Gm, A2m, or Km specificity when the overall sample was considered. However, significant different sex ratios were shown by patients' fnb positive and fnb negative genotypes, with a relative risk of 10.7 for this haplotype in males, suggesting that sex and Gm influence the penetrance of the HLA-linked genes. The significance of this finding is strengthened by the recent report that H-2 and Ig allotypes intervene in the genetic control of murine immune response to A-gliadin (M.F. Kagnoff, Nature 296:158, 1982).

Adult↗

PubMed2003

Colonia Tovar: the history of a semi-isolated Venezuelan population of German ancestry described by HLA class I genes.

The history of Colonia Tovar is very complex, being the home of descendants of only a small fraction of immigrants arriving to the South American continent from a specific region of Germany, with a restricted number of founders, small population size and consanguineous mating, experiencing isolation for 100 years, with later migrations, a low rate of population growth and a high mean number of children per couple. How complex is its genetic structure? Do the highly polymorphic HLA genes reflect its history and confirm the story of this population described by other genes? Several studies have been made in this population, but we describe for the first time the HLA Class I variability in the population of Colonia Tovar using PCR-SSOP. Random genetic drift, founder effect and gene flow could explain the HLA allele and haplotype frequencies observed in this population but alleles at the class I loci were insufficient to identify the German origin of the community established through history. This agrees with findings obtained testing other genetic systems (ACP, AK, ESD, G6PD, GLO, PGM, PGD, ALB, CP, HP, TF), but the HLA-typing results indicate that the original gene pool has been diluted due to gene flow from the surrounding Mestizo population.

Adolescent↗

PubMed1989

The usefulness of various polymorphisms in paternity testing. Experience with three southern African populations.

Genetic studies have been carried out on 1,059 cases (involving 3,177 blood samples) of disputed paternity. Seventeen polymorphic systems, representing 21 loci, have been used on all the cases and an additional 11 system (12 loci) were used when an exclusion on only one of the system was obtained. The overall rate of exclusion was 34.0% and the data were analysed according to the population from which the case came (white, 'coloured' or black). HLA is the most informative system in all three populations, followed by PGM1, with the rhesus blood group the next most useful in the whites and 'coloured's, whereas ABO is the next most useful in the blacks. The probability of excluding a man falsely accused of paternity was 99.1% in the black, 99.4% in the white and 99.7% in the 'coloured' populations. The data were also used to calculate the probability of paternity in the cases in which an exclusion could not be demonstrated; values of over 98% were found in 98.5% of whites, 98.8% of 'coloureds' and 90% of blacks; a further 9.1% of blacks gave values of 95.1 - 98.0%. The range of genetic markers, representing red cell antigen, red cell enzyme, serum protein and HLA polymorphisms used in this study, meets the requirements of an efficient paternity testing service.

Black People↗