RESUMO
The aetiology of Behçet's disease (BD) is still unknown, but genetic and environmental factors are involved. HLA-B*51 is considered a susceptibility marker and some MICA alleles have also been associated. Cytotoxic T lymphocytes have been suggested as responsible for BD lesions by engaging MICA through NKG2D surface molecules. In the present study, HLA-B and MICA alleles were typed by polymerase chain reaction using sequence-specific primers, in 165 healthy Spanish controls and 42 BD patients. In the healthy group, MICA*008 (28.48%), MICA*004 (17.58%), MICA*002 (14.24%) and MICA*009 (9.39%) were the predominant alleles and the most common haplotype was MICA*004-B*44 (12.12%). MICA*001 (5.15%), MICA*004, MICA*011 (4.54%) and MICA*018 (5.15%) were more frequent, and MICA*010 (1.81%) and MICA*008 were less prevalent than in other Caucasoid populations. Similar results have been reported in North African individuals and this could support the hypothesis of a common ancestral origin of both populations. The frequencies of MICA*009 and MICA*019 were significantly increased in our BD patients in comparison with controls: 22.62% versus 9.39% and 10.71% versus 1.81% respectively. The increase of MICA*019 had not been described in other BD cohorts, and it corroborates the genetic heterogeneity at MICA locus in BD patients. High-affinity MICA alleles for NKG2D were more frequent in controls than in patients. Moreover, high-affinity alleles were not found in homozygous BD patients. These results argue against the hypothesis of an autoaggressive response in BD patients through MICA-NKG2D interactions.
Assuntos
Síndrome de Behçet/genética , Síndrome de Behçet/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Polimorfismo Genético , Estudos de Casos e Controles , Frequência do Gene , Antígenos HLA-B/genética , Haplótipos , Humanos , Subfamília K de Receptores Semelhantes a Lectina de Células NK , Receptores Imunológicos/imunologia , Receptores de Células Matadoras Naturais , Espanha , População BrancaRESUMO
Common variable immunodeficiency disease (CVID) is a heterogeneous syndrome characterized by low immunoglobulin serum levels and recurrent bacterial infections. Several studies suggest that CVID patients have a polarized immune response towards a T helper type 1 phenotype (TH1). However, the factors causing the TH1 polarization remain to be determined in this disease. In the present study, serum interleukin (IL)-12, interferon (IFN)-gamma levels and the IL-12p40 and IFN-gamma gene were studied in CVID patients. Furthermore, we evaluate dendritic cells (DCs) compartment, myeloid dendritic cells (mDCs) and plasmocytoid dendritic cells (pDCs), which help to differentiate naive T cells preferentially into TH1 and TH2, respectively. The serum IL-12p40 subunit levels were increased significantly in CVID patients compared to healthy controls. We examined whether these elevated serum IL-12p40 levels are associated with IFN-gamma or IL-12p40 gene polymorphisms, or with new mutations in the IL-12p40 promoter gene. In our hands, no new mutations were found and gene polymorphisms frequencies in CVID patients were similar to the control population. In conclusion, the elevated serum levels of IL-12p40 found in our CVID patients were not related to these genetic variations. The DC compartment analysis did not show an imbalance between pDCs and mDCs, but revealed the presence of low numbers and percentage of both DC populations in CVID.
Assuntos
Imunodeficiência de Variável Comum/sangue , Células Dendríticas/imunologia , Interferon gama/sangue , Interleucina-12/sangue , Subunidades Proteicas/sangue , Contagem de Células Sanguíneas , Imunodeficiência de Variável Comum/genética , Regulação da Expressão Gênica/genética , Genótipo , Humanos , Interferon gama/genética , Interleucina-12/genética , Subunidade p40 da Interleucina-12 , Mutação , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Subunidades Proteicas/genética , Células Th1/imunologiaRESUMO
No disponible
No disponible
Assuntos
Humanos , Feminino , Imunodeficiência de Variável Comum/genética , Incontinência Pigmentar/genética , Incontinência Pigmentar/epidemiologia , Mutação , Infecções/genética , Doenças Genéticas Ligadas ao Cromossomo X/genéticaRESUMO
No disponible
Assuntos
Feminino , Lactente , Humanos , Incontinência Pigmentar/epidemiologia , Síndromes de Imunodeficiência/genética , Espanha/epidemiologia , Cromossomos Humanos X/genética , Inativação GênicaRESUMO
'Chueta' was the name given to the Catholic descendants of Jewish victims of the last Spanish Inquisition process in Majorca Island in the western Mediterranean. We have studied the allele distribution of HLA-A, -B, -Cw, -DRB1 and -DQB1 loci of 103 random, healthy, unrelated individuals belonging to the ancient Majorcan Jewish community, known locally as Chuetas, and 589 individuals from the Balearic population selected because of their typical Balearic - Majorca, Minorca or Ibiza - lineages and according to their ancestor's place of birth. Our aim was to establish the genetic relationship between Majorcan Chuetas, and Balearic and other Jewish and Mediterranean populations. Our results have shown that, to a remarkable extent, they have retained their biological identity, with a unique pattern, in terms of gene and haplotype frequencies, separate from the other populations of Majorca. The Chuetas were found to be more related to Moroccan and Libyan Jews than other Majorcans. Characteristic Jewish haplotypes, A26-B38-DRB1*13, A24-B38-DRB1*11, A1-B52-DRB1*15/16, were found in our study. Some peculiarities were observed in the distribution of common haplotypes among the three main Balearic Islands. The Ibizan population was genetically different from the other Balearic populations, with a high frequency of some haplotypes, for example, A29-Cw*16-B44-DRB1*07-DQB1*03; A1-Cw*07-B8-DRB1*03-DQB1*02. We also found a new haplotype, A25-Cw*12-B39-DRB1*11-DQB1*03(3.5%), in Ibizans and a more limited variability in the HLA alleles that were expressed, perhaps because of genetic isolation. The genetic diversity of the populations from Majorca and Minorca were similar and more related to the mainland Spanish population.
