RESUMO
One hundred and ten novel MHC-DRB gene exon 2 nucleotide sequences were sequenced in 96 monkeys from three owl monkey species (67 from Aotus nancymaae, 30 from Aotus nigriceps and 13 from Aotus vociferans). Owl monkeys, like humans, have high MHC-DRB allele polymorphism, revealing a striking similarity with several human allele lineages in the peptide binding region and presenting major convergence with DRB lineages from several Catarrhini (humans, apes and Old World monkeys) rather than with others New World monkeys (Platyrrhini). The parallelism between human and Aotus MHC-DRB reveals additional similarities regarding variability pattern, selection pressure and physicochemical constraints in amino acid replacements. These observations concerning previous findings of similarity between the Aotus immune system molecules and their human counterparts affirm this specie's usefulness as an excellent animal model in biomedical research.
Assuntos
Aotidae/imunologia , Genes MHC da Classe II/genética , Antígenos HLA-DR/genética , Polimorfismo Genético , Alelos , Sequência de Aminoácidos , Animais , Aotidae/genética , Sequência de Bases , Linhagem da Célula , Evolução Molecular , Éxons/genética , Antígenos HLA-DR/classificação , Cadeias HLA-DRB1 , Humanos , Dados de Sequência Molecular , Filogenia , Recombinação Genética , Seleção Genética , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
UNLABELLED: A total of 220 individuals were included in this study, 112 HIV-seronegative healthy individuals and 108 HIV-1-infected patients involving: 18 AIDS patients with Toxoplasmic encephalitis (AIDS-TE), 49 AIDS patients without TE, and 41 asymptomatic patients, were genotyping for DR and DQ loci by molecular biology techniques. Fisher's Exact test was used for statistical analysis. HLA-DQB*0402 and DRB1*08 alleles were associated with a high risk to develop opportunistic infections with neurological involvement, mainly Toxoplasma encephalitis in relationship with subjects healthy (OR = 20.43; Pc = 7.0 x 10(-6) and OR = 11; Pc = 2.6 x 10(-4), respectively); in relationship with AIDS no TE (OR = 6.98; Pc = 0.028 and OR = 4.85; P = 0.012, Pc = 0.14) and with patients in asymptomatic stage (OR = 61.50, Pc = 8.4 x 10(-6) and OR = 19.38; Pc = 3.9 x 10(-4)), respectively. CONCLUSIONS: It was concluded that the presence of HLA-DQB*0402 and DRB1*08 alleles in HIV-1-positive patients could be considered risk factors for developing neurological opportunistic infections, mainly Toxoplasmic encephalitis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/genética , Encefalite/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Toxoplasmose Cerebral/genética , Infecções Oportunistas Relacionadas com a AIDS/complicações , Argentina/epidemiologia , Estudos de Casos e Controles , Encefalite/complicações , Frequência do Gene , Predisposição Genética para Doença , HIV-1 , Antígenos HLA-DQ/classificação , Cadeias beta de HLA-DQ , Antígenos HLA-DR/classificação , Humanos , Fenótipo , Toxoplasmose Cerebral/complicaçõesRESUMO
We explored a possible role of HLA class II genes in determining the susceptibility to Trypanosoma cruzi infection as well as in the development of chagasic heart disease in a rural mestizo population from Arequipa (Southern Peru). HLA-DRB1 and DQB1 polymorphisms were determined in 85 seropositive (asymptomatic, n=52; cardiomyopathic, n=33) and 87 seronegative individuals. We observed that the DRB1*14-DQB1*0301 haplotype correlates with not having T. cruzi infection in a highly endemic area (OR= 0.26 (0.124.63); Pc=0.01). This protective association is a dominant trait. We found no differences in the allelic or haplotypic distributions we examined between asymptomatic and cardiomyopathic patients in this population. Our data offer indirect but compelling evidence that polymorphism in HLA region is involved in a differential susceptibility to T. cruzi chronic infection.
Assuntos
Cardiomiopatia Chagásica/genética , Doença de Chagas/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Adolescente , Adulto , Idoso , Animais , Cardiomiopatia Chagásica/imunologia , Doença de Chagas/imunologia , Doença Crônica , Suscetibilidade a Doenças/imunologia , Frequência do Gene , Predisposição Genética para Doença/genética , Antígenos HLA-DQ/classificação , Cadeias beta de HLA-DQ , Antígenos HLA-DR/classificação , Cadeias HLA-DRB1 , Haplótipos , Humanos , Pessoa de Meia-Idade , Peru , Polimorfismo Genético , Trypanosoma cruziRESUMO
The aim of this study was to elucidate whether peritoneal macrophage (pMO) alterations are a generalized feature in all stages of endometriosis and the effect of hormonal treatment on this leukocyte population. For this purpose we quantified the number of pMO, the expression of HLA-DR antigen (pMO DR+), percentages of pMO that reduced nitro-blue tetrazolium (pMO NBT+), and interleukin-1 (IL-1) and prostaglandin E2 (PGE2) production by pMO from patients with early (stages I/II) and advanced (stages III/IV) endometriosis, we also analyzed some of these properties in pMO from patients which had been treated for 6 months with 800 mg/day of Danazol or gonadotropin releasing hormone agonist (GnRHa). We found that there were a significant increase of the pMO number in both types of patients, though the highest values were obtained in early endometriosis (p < 0.001). Percentages of pMO DR+ were decreased in all patients (p < 0.01) while percentages of pMO NBT+ were significantly increased. Production of IL-1 by early and advanced endometriosis pMO were considerably enhanced. PGE2 release was not altered in early endometriosis pMO but, in advanced endometriosis, pMO PGE2 levels were 100-fold higher than control values. In posttreatment patients, the number of pMO and percentage of pMO NBT+ were similar to early endometriosis patients, though the percentage of pMO DR+ was within the normal range. We conclude that the pMO population, as well as IL-1 and PGE2 production, were altered in all stages of endometriosis, and that these changes could be involved in the pathogenesis of endometriosis and associated infertility. Hormonal treatments do not reverse the pMO changes.
Assuntos
Endometriose/imunologia , Macrófagos/imunologia , Adulto , Danazol/uso terapêutico , Dinoprostona/metabolismo , Endometriose/tratamento farmacológico , Antagonistas de Estrogênios/uso terapêutico , Feminino , Hormônio Liberador de Gonadotropina/agonistas , Antígenos HLA-DR/classificação , Humanos , Interleucina-1/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Macrófagos/classificação , Macrófagos/efeitos dos fármacos , Nitroazul de Tetrazólio/metabolismo , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , FenótipoRESUMO
Serological HLA types (A, B, C, DR and DQ loci) were studied in five different Indian tribes (Cubeo, Tucano, Coreguaje, Embera and Noanama) belonging to two distinct linguistic families. For all the MHC loci, the range of variation among the five tribes was enormous. Two tribes, Cubeo and Tucano, showed a wide spectrum of antigenic specificities which seemed to be due to admixture from non-tribal groups, while in the other three tribes the polymorphisms of various HLA loci showed restricted distributions. The gene frequency data, when converted to a kinship matrix and a two-dimensional eigenvector plot, indicated that members of the same linguistic family tend to have greater genetic affinity.
Assuntos
Antígenos HLA/genética , Indígenas Sul-Americanos/genética , Colômbia , Feminino , Frequência do Gene , Antígenos HLA/classificação , Antígenos HLA-A/classificação , Antígenos HLA-A/genética , Antígenos HLA-B/classificação , Antígenos HLA-B/genética , Antígenos HLA-C/classificação , Antígenos HLA-C/genética , Antígenos HLA-DQ/classificação , Antígenos HLA-DQ/genética , Antígenos HLA-DR/classificação , Antígenos HLA-DR/genética , Humanos , Linguística , MasculinoRESUMO
The association of multiple sclerosis (MS) with the HLA class II loci DR and DQ was investigated in populations of Asian Indian and Afro-Caribbean ethnic origin, resident in the United Kingdom. The putative haplotype, DRB1*1501.DQA1*0102.DQB1*0602, was weakly positively associated with MS in both races. The overall contribution to disease susceptibility of this marker was small. Over 80% of the MS patients in both racial groups did not possess this haplotype. The data suggest that other genetic and/or environmental factors may be more important in predisposing to MS in these two races. Our study also raises the possibility that genetically distinct forms of the disease may be expressed in white Caucasian and non-Caucasian populations.
Assuntos
Genes MHC da Classe II/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Esclerose Múltipla/genética , População Negra/genética , Estudos de Casos e Controles , DNA/sangue , Sondas de DNA de HLA , Antígenos HLA-DQ/classificação , Antígenos HLA-DR/classificação , Humanos , Índia/etnologia , Jamaica/etnologia , Esclerose Múltipla/etnologia , Reação em Cadeia da Polimerase , Reino Unido/epidemiologia , População Branca/genéticaRESUMO
The association of multiple sclerosis (MS) with the HLA class 11 loci DR and DQ was investigated in populations of Asian Indian and Afro-Caribbean ethnic origin, resident in the United Kingdom. The putative haplotype, DRB1*1501.DQA1*0102.DQBI*0602, was weakly positively associated with MS in both races. The overall contribution to disease susceptibility of this marker was small. Over 80 percent of MS patients in both racial groups did not possess this haplotype. The data suggest that other genetic and/or environmental factors may be more important in predisposing to MS in these two races. Our study also raises the possibility that genetically distinct forms of the disease may be expressed in white Caucasian and non-Caucasian populations (AU)