RESUMO
Two novel HLA-B alleles, B*07:299 and B*35:350, were characterized by genomic full-length sequencing.
Assuntos
Alelos , Antígenos HLA-B/genética , Sequência de Aminoácidos , Antígenos HLA-B/química , Humanos , Domínios ProteicosRESUMO
Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFß [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1ß [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFß, IL10, IL6, IL1α, IL1ß, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFß, IL10, IL6 and IL1α, IL1ß, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development.
Assuntos
Colite Ulcerativa/genética , Doença de Crohn/genética , Citocinas/genética , Inflamação/genética , Adolescente , Adulto , Feminino , Genótipo , Humanos , Inflamação/imunologia , Masculino , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
Tumour necrosis factor alpha (TNF-α) has an important role in inflammatory response. Alterations in the regulation of TNF-α have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF-α inhibitors. Polymorphisms in the TNF-α promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF-α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti-TNF-α treatment. DNA samples from patients with IBD and controls were screened for TNF-α -238G/A (rs361525) and -308G/A (rs1800629) SNPs by PCR-SSOP using a microbeads luminex assay and compared with response to TNF-α inhibitors. There were not statistical differences in -238G/A and -308G/A allele and genotype frequencies between patients. However, we found an increased frequency of -308A allele and -308GA genotype in these nonresponders patients to TNF-α inhibitors with respect to responders patients (Pc < 0.05). This -308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF-α inhibitors. TNF-α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF-α genotypes may be involved in the different responses to TNF-α inhibitor treatment in Spanish patients with IBD.
Assuntos
Doenças Inflamatórias Intestinais/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/genética , População Branca/genética , Adolescente , Adulto , Alelos , Criança , Feminino , Frequência do Gene , Genótipo , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Espanha , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: There is no consensus about the impact of thresholds of complement-fixing antibody assays. Recently, a C1q-SAB assay has been developed to identify complement-fixing HLA antibodies with high sensitivity and specificity. Our aim was to determine the correlation between IgG single antigens beads (SAB) and C1q-SAB assay results among patients on the renal waiting list. PATIENTS AND METHODS: Serum samples from immunized renal waiting list patients as well as negative and positive controls were valided by Luminex (LMX). These sera, which were positive for 166 antibody specificities, were tested for HLA class I in parallel by LMX-IgG and LMX-C1q. RESULTS: Comparison of antibody detection revealed no correlation based on median fluorescent intensity (MFI), levels between the IgG SAB and the C1qSAB assay (P > .05). IgG-positive sera with MFIs as low as 700 were able to fix C1q, whereas other sera with MFIs as high 14,500 did not. Furthermore, there appeared to be disparities in the profiles of class I antigens able to fix C1q-SAB. In our series, only 34% class I IgG SAB antibodies were also C1qSAB+. In several patients, we detected C1qSAB+ against IgGSAB- that was surely due to IgM antibodies. So, the C1qSAB assay detected IgM antibodies that fix complement. CONCLUSION: These data suggested that the C1q-SAB assay could be an important method to evaluate pretransplant virtual crossmatch and to define nonpermitted specificities (C1q-fixing) in kidney transplantation.
