Assuntos
Metionina , Sinais Direcionadores de Proteínas , Humanos , Alelos , Racemetionina , Antígenos HLA-B/genéticaRESUMO
Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.
Assuntos
Aborto Habitual , Infertilidade , Gravidez , Humanos , Masculino , Feminino , Antígenos HLA-C/genética , Estudos Retrospectivos , Motivos de Aminoácidos , Estudos de Casos e Controles , Aborto Habitual/genética , Receptores KIR/genética , Infertilidade/genética , BiomarcadoresRESUMO
Sequence and expression analysis of the HLA-DRB1*10:38 allele.
Assuntos
Cadeias HLA-DRB1 , Humanos , Cadeias HLA-DRB1/genética , Sequência de Bases , AlelosRESUMO
BACKGROUND: Immigrants represented 21.8% of cases in a Spanish cohort of hospitalised patients with COVID-19, a proportion exceeding the percentage of immigrants in that area's total population. Among the ethnic-related genetic risk factors for COVID-19, human leukocyte antigen (HLA) genotypes in diverse populations might bias the response to SARS-CoV-2 infection and/or progression. Similarly, genetic differences in natural killer-activating and inhibitory receptors could play a role in the immune system's response to the viral infection. METHODS: We characterised HLA alleles and KIR genes in 52 Ecuadorian patients hospitalised for moderate and severe COVID-19 and 87 Ecuadorian controls from the general population living in the same area. RESULTS: There was a significantly increased frequency of the HLA-B*39 antigen and the activating KIR2DS4 receptor in the presence of its HLA-C*04 ligand in the COVID-19 group when compared with the control group. In contrast, there was a significant reduction in the frequency of carriers of KIR2DL1 and of the KIR3DL1/Bw4 receptor/ligand combination among COVID-19 group. On the other hand, HLA-A*24:02 and HLA-DRB1*09:01 alleles showed significantly lower frequencies specifically in the severe COVID-19 group. CONCLUSION: HLA-B*39 alleles might be genetic risk factors for developing COVID-19 in Ecuadorian individuals. In the presence of its ligand C*04, the natural killer-activating receptor KIR2DS4 might also increase the risk of developing COVID-19, while, in the presence of HLA-Bw4 alleles, the inhibitory receptor KIR3DL1 might play a protective role. Patients with COVID-19 who carry HLA-A*24:02 and HLA-DRB1*09:01 alleles might be protected against more severe forms of COVID-19.
Assuntos
COVID-19 , Receptores KIR , Humanos , Cadeias HLA-DRB1/genética , Ligantes , Fatores de Proteção , Equador/epidemiologia , Receptores KIR/genética , COVID-19/genética , SARS-CoV-2 , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos HLA-B/genética , Genótipo , Antígenos HLA-A/genéticaRESUMO
Characterization of six novel HLA alleles by next-generation sequencing.
Assuntos
Antígenos HLA-A , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Antígenos HLA-A/genética , Cadeias HLA-DRB1/genéticaRESUMO
Genomic full-length characterization of the HLA-DQB1*03:25:01 allele.
Assuntos
Antígenos HLA-DQ , Humanos , Antígenos HLA-DQ/genética , Alelos , Cadeias beta de HLA-DQ/genética , HaplótiposRESUMO
Characterization of two novel HLA class I null alleles.
Assuntos
Antígenos HLA-B , Nucleotídeos , Humanos , Alelos , Mutação , Antígenos HLA-B/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
The novel HLA-DQB1*04:02:01:16Q allele showing a point mutation in the intron 3.
Assuntos
Mutação Puntual , Alelos , Cadeias beta de HLA-DQ/genética , Humanos , ÍntronsRESUMO
Characterization of the novel HLA-C allele, HLA-C*07:1000.
Assuntos
Antígenos HLA-C , Recombinação Genética , Alelos , Genes MHC Classe I , Antígenos HLA-C/genética , HumanosRESUMO
Six novel HLA alleles were characterized in the Spanish population.
Assuntos
Alelos , Frequência do Gene , Cadeias beta de HLA-DP/genética , HumanosRESUMO
Five new HLA class I alleles were characterized by next-generation sequencing.
