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Z Layrisse

Publications and source records attributed to Z Layrisse.

At least 37 records · Page 2Linked to original sources
PubMed1997

Generation of the HLA-B35, -B5, -B16, and B15 groups of alleles studied by intron 1 and 2 sequence analysis.

HLA-B is the most polymorphic of the major histocompatibility complex classical class I loci. This polymorphism is mainly in exons 2 and 3, which code for the molecule's alpha 1 and alpha 2 domains and include the antigenic peptide binding site. Recent studies have indicated that not only exons but also the intron 2 region may be involved in the generation of certain HLA-B alleles such as B*3906 and B*1522. To study the degree of intron 2 participation and the mechanisms that generate polymorphism at the HLA-B locus, intron 1 and 2 sequences from the HLA-B35, -B5, -B16 and -B15 groups of alleles were obtained. A group-specific intronic polymorphism was found: namely, B*5301 shows intron 1 and 2 sequences identical to those found in all B35 alleles studied. On the other hand, B*5101 and B*52012 show the same intron 1 and 2 sequences and their intron 1 is the same as that found in the B35 group. This suggests that B5 and B35 groups of alleles may have arisen from a common ancestor. All known B16 alleles show the same introns 1 and 2, with the exception of B*39061 and B*39062, and all B15 alleles also bear the same introns 1 and 2, with the exception of B*1522. Variability at intron 1 is more restricted than at intron 2, and the use of intron 1 for HLA-B allele phylogenetic analysis is better for grouping alleles of a postulated common origin. In conclusion, there is a remarkable conservation of intronic sequences within related HLA-B alleles, which probably reflects a common origin and perhaps a selective force avoiding DNA changes. Intronic sequences are also potentially useful to design DNA typing strategies.

Alleles↗
PubMed1997

HLA class I and class II allele and haplotype distribution in the Venezuelan population.

Population studies represent an integral part, and a necessary link in a complex chain of host-pathogen interactions, disease pathogenesis, and major histocompatibility complex polymorphism. HLA class I and class II allele and haplotype distributions among Venezuelan mestizos were determined. Genes of Mongoloid, Negroid, and Caucasoid origin have created a distinctive human leukocyte antigen (HLA) genetic profile in this hybrid mestizo population that will influence HLA and disease association studies. The predominant HLA-B DQA1 DQB1 DRB1 haplotype is HLA-B44 DQA1*0201 DQB1*0201 DRB1*0701 (5.3%). It is noteworthy that the HLA-A3 B7 DR2 and the HLA-A1 B8 DR3 linkage groups, which are part of conserved or ancestral haplotypes, the last one associated with a wide range of autoimmune diseases and immune abnormalities in apparently healthy subjects, show low incidence among Venezuelan mestizos. This fact may be useful for future HLA and disease association studies and for localization of genes involved in immune regulation associated with these haplotypes.

Adult↗
PubMed1997

The novel HLA-DRB1*0807 allele is present in a Carib Amerindian population: the Yucpa.

Nucleotide sequences of five novel HLA-DRB1*08 alleles have been recently reported but their frequency in different populations is still unknown. The presence of DRB1*08 variants among Carib-speaking Yucpa Amerindians of the Perijá Range in the border between Colombia and Venezuela was tested by PCR-DNA typing. DRB1*0807 was the only DRB1*08 variant found in this population with a frequency of 0.1250. Until very recently, DRB1*0802 was the predominant DRB1*08 allele present among full-blooded Amerindians, but in the last 3 years DRB1*0804 has been found in 2 South American tribes and *0811 in 2 North American tribes. The description of a new functional DRB1*08 variant in Amerindians suggests that extensive gene polymorphism among Amerindians might not be limited to the HLA-B Class I locus.

Alleles↗
PubMed1997

[High- and low-risk molecular sequences in autoimmune diseases. An analysis of type I diabetes in Latin America].

Type I diabetes is an autoimmune and a polygenic disease, in which MHC-class II genes contribute to 48% of the disease. The aim of the present study, is to provide a guideline to understanding the molecular association of these genes, through the immunogenetic analysis of 3 Latin american mestizo populations. We included 606 individuals, 349 patients with DMDI and 257 healthy controls coming from 3 geographical areas: Mexico City, Mexico; Caracas, Venezuela and Medellin, Colombia. The results clearly indicate that in mestizo groups, the diabetogenic haplotypes are from mediterranean ancestry, while protection is due to Amerindian genes. It was demonstrated that the relevant sequences for IDDM expression are located to DRB1 and DQB1 loci with a minimal contribution of DQA1 residues. The sequences determining peptide recognition and the induction of TH1 cells mediating the cellular autoimmune response are in positions DRB1-57 and 74 (an aspartic acid and a glutamic acid respectively, confer protection), modulated by D-57 in the DQ, 8 chain. These data show that DRB1-DQB1 haplotypes are central for IDDM expression and open new pathways for the disease management.

Adolescent↗
PubMed1997

Common Caucasoid HLA-A1B8DR3 linkage group and immune responsiveness in a hybrid Venezuelan population: preliminary data.

A study performed on Venezuelans reveals a correlation between the common Caucasoid linkage group HLA-A1 B8 (A*0101, B*0801, DR3-) and increased lymphoproliferative activity stimulated by several concentrations of phytohemagglutin and concanavalin A in comparison to the group of persons possessing either the HLA-A1 (A*0101) antigen or the HLA-B8,DR3 (B*0801,DRB1*03012) haplotype. The increased lymphoproliferative activity was simultaneously present with increased CD16 cell counts and decreased CD3 and total mononuclear counts. A further comparison of lymphocyte population and subpopulation counts in peripheral blood and serum Ig G,A,M levels in the HLA-A1+ B8+ versus the HLA-A1-B8-high-responder individuals revealed increased CD16 cell counts and IgM levels in persons with the common Caucasoid haplotype (HLA-A1 B8). The data may suggest that some of the genes responsible for these levels or genes controlling their expression could be localized in or along the length of the common Caucasoid haplotype HLA-A1 B8 between the A and B loci of the MHC.

Adult↗
PubMed1995

Strong association between major histocompatibility complex class I antigens and immune aberrations among healthy Venezuelans.

Immune reactivity indicators studied among 55 unrelated Venezuelan mestizo subjects included lymphoproliferative response to polyclonal mitogen (PHA, Con A, PwM) stimulation, NK cell activity, and enumeration of peripheral blood mononuclear cells. HLA-A, -B, -C, -DR, and -DQ antigens were determined by serologic typing. A strong association between impairment of the parameters studied and MHC class I antigens A11 and A3 was found. Subjects with decreased suboptimal (0.5 micrograms/ml) PHA response as well as decreased optimal (0.5 micrograms/ml) Con A response showed high incidence of HLA-A11 antigen (RR = 81, p = 0.001, pc = 0.021 and RR = 54, p = 0.0029, respectively). Subjects with decreased suboptimal (0.5 micrograms/ml) PHA response HLA-A11- with only one exception, were either HLA-A1+ or HLA-A3+. These antigens belong to the same CREG, share public epitopes, and have low incidence in the Venezuelan mestizo population. Six of 10 persons with decreased CD16 subset count (5.17% +/- 0.23% vs 11.69% +/- 0.44%) had HLA-A3 antigen (RR = 17, p = 0.001, pc = 0.021). The data indicate a possible contribution of HLA-A11,A3, molecules through their private and/or public determinants to immune response aberrations which under certain conditions may result in development of diseases.

Adult↗
PubMed1995

Extended HLA haplotypes among the Bari Amerindians of the Perija Range. Relationship to other tribes based on four-loci haplotype frequencies.

Extended HLA haplotypes among Bari Amerindians living at the Perija Range on the limits between Colombia and Venezuela have been defined using serology for class I, electrophoresis and immuno-fixation for Bf and C4, and PCR-SSO for class II loci typing. Haplotypes were assigned based on family studies and gene frequencies were calculated using a subset of less related subjects selected from the genealogy. No rare class III variants were observed, but the characteristic low HLA diversity of isolated Amerindians populations present also in the Bari extends to Bf and C4. Thus there were only 22 different haplotypes segregating in families when nine loci were considered. All of them except three carried Bf*S, C4A*3, C4B*1. The null allele C4A*Q0 reached a frequency of 0.147 and was predominantly present in A24 Cw7 B39 DRB1*0411 haplotypes. In contrast to what has been reported using HLA alleles or class I haplotype frequencies and other isolated South American tribes, genetic distance estimates based on A-Cw-B-DR haplotype frequencies show a closer relationship between the two linguistically but geographically distant Venezuelan tribes, the Bari and the Warao, as compared to two culturally different Brazilian populations. The information reported here will be useful for identifying ancestral haplotypes in native peoples of America, for population comparison, and for discussing the differential influence of MHC haplotype diversity and population survival when similar data on other Amerindian tribes becomes available.

Alleles↗
PubMed1995

Evolutionary relationships between black South American and African populations.

Data related to ten protein genetic loci expressed in blood obtained from four South American black populations were compared with data from seven African countries. Estimates of admixture among South American blacks were revised, and several indexes of gene diversity and genetic distances between the 11 populations were calculated. The admixture values and genetic relationships observed among the South American black communities conform well with those expected on historical grounds, and they show only moderate reductions in genetic diversity.

Africa↗
PubMed1994

HLA-DQA1 and DQB1 allele and genotype contribution to IDDM susceptibility in an ethnically mixed population.

HLA-DRB1, DQA1 and DQB1 alleles have been determined in 42 families with one IDDM proband and 64 healthy controls, by oligotyping (PCR-SSO) using primers and probes from the XI International Histocompatibility Workshop. A positive DRB1*03 and DRB1*04 association with the disease was observed, whereas DRB1*11 and DRB1*07 showed negative association but 19% of patients carried DRB1 alleles different to DRB1*03 or *04. When single alleles were considered, DQA1*03 showed the strongest association with susceptibility to the disease (RR = 8.2, Pc = 0.00001) but this association was outgrown by 2 and 3 allele combinations, with genotype DRB1*04-DQA1*03-DQB1*0302/DRB1*03- DQA1*0501- DQB1*0201 showing the strongest association (RR = 28, Pc = 0.002). Application of the relative predispositional effect (RPE) method to our data, revealed a further susceptibility risk provided by the DRB1*13-DQA1*0102-DQB1*0604 haplotype once DR3 and DR4 haplotypes were removed. When DQA1-DQB1 genotypes were analysed for presence of Arg 52 (DQ alpha) and absence of Asp 57 (DQ beta), genotypes SS/SS were found significantly increased in diabetics. Interestingly, one of the strongest associations with the disease was observed with the DQA1*03-DQB1*0201 combination encoded mainly by genes in trans (RR = 11.7 Pc = 0.00004). These observations and their comparison with DR-DQ haplotypes in more homogeneous ethnic groups support the stronger influence of the DQ molecule rather than the individual DR or DQ alleles in the susceptibility to IDDM. They also emphasize the need for detailed HLA haplotype studies in non-Caucasian and ethnically mixed populations to gain further insight into the nature of genetic and environmental factors contribution to autoimmunity.

Alleles↗
PubMed1991

Alleles at four HLA class II loci determined by oligonucleotide hybridization and their associations in five ethnic groups.

The use of polymerase chain reaction (PCR) and oligonucleotide hybridization offers a new approach for the definition of HLA class II alleles. It has been possible to determine 43 alleles of DRB1, four of DRB3, two of DRB4, four of DRB5, eight of DQA1, and 14 of DQB1. These alleles are inherited together in members of families and form closely associated groups which are found repeatedly and in characteristic patterns in different populations. We have determined the HLA class II alleles and analyzed their association in 431 healthy unrelated subjects including 161 North American Caucasians, 53 Latin Americans, 61 Blacks, 88 Chinese, and 68 Israeli Jews. For-locus haplotypes (DRB1; DRB3/4/5; DQA1; DQB1) were derived from 79 B cell lines and the analysis of segregation in 34 nuclear families. The B-cell lines yielded 37 and the families showed the same, and 20 other, haplotypic combinations. In addition to these 57 haplotypes, associated alleles were assigned in the unrelated panels following certain rules. The resulting haplotypes were assigned to groups known to share associated alleles. The groups were: 1) DR1, DR2, and DRw10 (13 haplotypes); 2) DR3 and DRw6 (26 haplotypes); 3) DR5 and DRw8 (24 haplotypes); 4) DR4, DR7, and DR9 (24 haplotypes). Their distribution in populations with different ethnic backgrounds was analyzed. The expressed DRB4 allele and its null mutant were determined by PCR and oligonucleotide hybridization. The different DR7 haplotypes resulting from these determinations were analyzed in a panel of 130 North American Caucasoids. This comprehensive analysis of class II HLA haplotypes in human populations should be useful in understanding the role of these genes and in various applications including anthropology, disease susceptibility, and transplantation of allogeneic organs and tissues.

Alleles↗
PubMed1991

Immunogenetics of human American cutaneous leishmaniasis. Study of HLA haplotypes in 24 families from Venezuela.

Twenty-four families with one or multiple cases of localized cutaneous leishmaniasis (LCL) from an endemic region with the highest incidence of LCL in Venezuela were typed from HLA-ABC, DR, DQ antigens and complement factors. The parental HLA haplotypes segregated at random among healthy and affected siblings but in backcross families significantly higher frequencies of HLA-A28 (p = 0.0018), -Bw22 (p = 0.0122), or -DQw8 (p = 0.0364) were present in affected compared to healthy siblings. HLA-B15 showed a higher frequency (p = 0.0062) among the latter group. Haplotypes Bw22CF31 (p = 0.0076) and Bw22DRw11DQw7 (p = 0.0163) were also significantly more frequent in affected compared to healthy siblings and A2Cw- (p = 0.0445) among the latter. No HLA genetic linkage with a putative LCL susceptibility gene(s) could be demonstrated in this study. A case/control comparison of 26 unrelated LCL patients (one proband from each family) and healthy individuals of the same ethnic origin confirmed the association of HLA-Bw22 (pc = 0.048) and -DQw3 (pc = 0.036) with LCL. The relative risk reached 12.5 for Bw22 and 4.25 for DQw3 with ethiologic factors of 0.17 and 0.64, respectively. HLA-DQw3 apparently makes the major contribution as a genetic risk factor for LCL at the population level.

Female↗
PubMed1991

[Monoclonal antibodies and T-cell clones against HLA antigens: production and characterization].

The production and characterization of 21 monoclonal antibodies (MoAbs) resulting from the immunization of Balb/c mice with human lymphoblastoid cell lines is reported. Twelve MoAbs seem to be detecting an HLA polymorphic determinant. Four MoAbs are recognizing monomorphic Class I molecules and another MoAb detects HLA Class II molecules. These results were confirmed by ELISA, cytotoxicity, immunofluorescence and immunoprecipitation. Class and subclass of the MoAbs were assessed by Ouchterlony analysis. Twenty two T cell clones were additionally generated by limiting dilution of lymphocytes stimulated by allogeneic peripheral blood lymphocytes on mixed lymphocyte cultures. Five of these clones were characterized, testing each one for its ability to proliferate in response to a panel of lymphoblastoid cell lines. It was found that they detect the HLA-A9, A23, A29-31, Bw62 and DR7 specificities respectively. These results indicate that the generation of cellular monoclonal reagents is apparently more productive than the generation of murine MoAbs specific for polymorphic variants of HLA antigens.

Animals↗
PubMed1988

Unique HLA-DR/DQ associations revealed by family studies in Warao Amerindians. Haplotype and homozygosity frequencies.

HLA-A, Cw, B and A, Cw, B, DR genotypes have been assigned, respectively, to 318 and 175 Warao Amerindians belonging to 73 sibships, who were tested with International Histocompatibility Workshop reagents. Only 33% of the theoretically possible three-loci and 7% of the possible four-loci haplotypes were found, with 10 and 6 of them accounting, respectively, for 75% of the total observed. This limited haplotype variability, expected in an inbred population, was not accompanied by either an increased or a decreased frequency of homozygous individuals, as demonstrated by population and family analysis. Inheritance of five HLA loci haplotypes in 20 families showed the expected distribution of parental haplotypes in sibling pairs. The study revealed DR2sh (DRw16), DR4 and DRw6 in association with DQw7, and DRw8 with DQw4, and significant positive linkage disequilibria between Bw62 CW1, B51 DRw16, B39 DR4, Bw62 DRw6, and DRw8 DQw4. The DR2-DQw7 and DRw6-DQw7 associations and the first three paired loci disequilibria mentioned are described for the first time in Amerindians and have not yet been found among Japanese, Negroid, or Caucasoid populations.

Gene Frequency↗
PubMed1988

A T cell clone defining a common DP/DR determinant in strong linkage disequilibrium with HLA-A9.

Clone F-7 was generated by limiting dilution of lymphocytes stimulated by allogeneic PBL on MLC. Priming against the A23, Cw6, B45, DR7, DRw53, DQw2 haplotype was performed between two HLA haploidentical first degree relatives. The clone was tested for its ability to proliferate in response to a panel of 38 homozygous B lymphoblastoid cell lines plus three local T cell lines. It showed a pattern of reactivity corresponding to HLA-A9 specificity (r = 1) and presented a concomitant cytotoxic activity. Phenotypically, this clone consisted entirely of CD4 cells, as determined by indirect immunofluorescence. Its reactivity was completely blocked by anti-DR (GSP4.1, PL8, L243) and anti-DP (B7/21, PL15) Mo-Abs, whereas anti-DQ (1A3, TU22) and anti-class I (w6/32, BB7.7) Mo-Abs and anti-A9 antibodies did not inhibit its reactivity. These results may suggest that clone F-7 could recognize a DP specificity sharing common determinants with DR, which occurs in linkage disequilibrium with HLA-A9.

Antibodies, Monoclonal↗