ABSTRACT
HLA-B*15:04:04 differs from HLA-B*15:04:01 by one nucleotide at codon 238 (gat > gac).
Subject(s)
Alleles , Blood Donors , Exons , HLA-B15 Antigen/genetics , Laboratory Proficiency Testing/standards , Point Mutation , Base Sequence , Blood Transfusion , Brazil , Codon/chemistry , HLA-B15 Antigen/immunology , Haplotypes , Histocompatibility Testing , Humans , Male , Middle Aged , Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNAABSTRACT
HLA-A*02:481 differs from HLA-A*02:01:01:01 by one nucleotide and was found in four unrelated Brazilians.
Subject(s)
Alleles , HLA-A2 Antigen/genetics , Base Sequence , Brazil , Female , HLA-B15 Antigen/genetics , HLA-C Antigens/genetics , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Humans , Male , Molecular Sequence DataABSTRACT
The aim of this study was to investigate association of human leucocyte antigens (HLA)-DRB1 and DQB1 polymorphisms with hepatitis C virus (HCV) infection and with the occurrence of severe liver fibrosis/cirrhosis in chronically infected patients. Ninety-nine white patients, from southeast Brazil, with confirmed HCV chronic infection were included in the study. Severe fibrosis/cirrhosis (METAVIR scores F3-F4) was present in 49 patients. HLA-DRB1 specificities and DRB1*11 and DQB1* alleles were determined by PCR-SSP, and their frequencies were compared between patients and a control group of 103 healthy white Brazilian individuals. The results confirmed previous reports of the association of DRB1*11 and DQB1*03 with protection from chronic HCV infection, but did not confirm their association with protection from severe fibrosis/cirrhosis. Furthermore, the results suggested that the polymorphic sites on HLA molecules responsible for protection from chronic HCV infection are encoded not only by the DRB1*1101 and DQB1*0301, as suggested in the literature, but also by other DRB1*11 and DQB1*03 alleles. Thus, we hypothesized that the common polymorphic residues shared by different DRB1*11 and/or DQB1*03 alleles might be responsible for selection of viral epitopes for presentation to CD4(+) T cells, leading to an efficient immune response against the virus.
Subject(s)
Genes, MHC Class II , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Hepatitis C, Chronic/immunology , Adolescent , Adult , Aged , Alleles , Brazil , CD4-Positive T-Lymphocytes , Epitopes , Female , HLA-DQ beta-Chains , HLA-DRB1 Chains , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/pathology , Humans , Liver Cirrhosis/immunology , Liver Cirrhosis/virology , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, GeneticABSTRACT
HLA-B*52:21 differs from the closest, HLA-B*52:01:02, by two nucleotides (CTG â TGG), leading to an amino acid substitution from Leu to Trp at codon 156.
Subject(s)
Alleles , Amino Acid Substitution , Codon/genetics , HLA-B Antigens/genetics , Base Sequence , Brazil , Humans , Molecular Sequence DataABSTRACT
Human leucocyte antigen (HLA)-B*4509 differs from the closest HLA-B*4502 by three nucleotides that lead to changes of Tyr113His, Asn114Asp and Phe116Ser. HLA-B*5212 differs from HLA-B*520101 by a single nucleotide substitution, leading to a change of Asn114Asp.
Subject(s)
HLA-B Antigens/genetics , Alleles , Amino Acid Substitution , Base Sequence , Brazil , DNA/genetics , DNA Primers/genetics , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Sequence Homology, Nucleic AcidABSTRACT
It was recently shown that IL-2 gene single nucleotide polymorphism (SNP) at position -330 (G-->T) is related to in vitro cytokine production levels, with the T/T and T/G genotypes being associated with low production and the G/G genotype associated with high production. The objective of this study was to investigate a possible influence of this polymorphism on renal and cardiac allograft outcomes. IL-2 SNP G-T (-330) was determined by PCR-RFLP in 67 recipients of heart allografts and in 63 recipients of renal grafts from HLA-haplo-identical, related donors. A higher frequency of the T/T genotype was observed in renal transplant patients who experienced at least one acute rejection episode during the first 3 months after transplantation than in those without rejection during this period (80% vs 49%, respectively, P <.05). Accordingly, the same genotype tended to be more frequent in renal recipients with a 6-month serum creatinine level above 1.5 mg/dL (median value for the whole group of kidney recipients) than in patients with lower creatinine levels (79% vs 45%, P <.08). Regarding cardiac transplant recipients, no associations were observed concerning acute rejection or graft survival. The finding of the association of T/T but not T/G genotype with acute kidney rejection was unexpected considering that both genotypes were shown to be associated with equal (low) IL-2 in vitro production. Further studies are necessary not only to dissect the nature of IL-2 T/T genotype association with kidney rejection, but also to explain why this genotype does not apparently influence cardiac allograft outcome.
Subject(s)
Heart Transplantation/immunology , Interleukin-2/genetics , Kidney Transplantation/immunology , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Acute Disease , Creatinine/blood , Genotype , Graft Survival/immunology , Histocompatibility Testing , Humans , Phenotype , Polymorphism, Restriction Fragment Length , Time Factors , Treatment OutcomeSubject(s)
Gene Expression Regulation , Heart Transplantation/physiology , Lymphocyte Culture Test, Mixed , Biopsy , Cells, Cultured , DNA Probes , Gene Expression Regulation/immunology , Graft Rejection/epidemiology , Graft Rejection/immunology , Heart Transplantation/immunology , Heart Transplantation/pathology , Humans , Lymphocytes/immunology , Regression AnalysisSubject(s)
Graft Rejection/epidemiology , Heart Transplantation/immunology , Membrane Proteins/genetics , Receptors, Nerve Growth Factor/genetics , Receptors, Tumor Necrosis Factor/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics , Adult , Antigens, CD/genetics , CD27 Ligand , Gene Expression Regulation/immunology , Graft Rejection/immunology , Humans , Membrane Glycoproteins/genetics , Membrane Glycoproteins/immunology , Receptors, Nerve Growth Factor/immunology , Receptors, Tumor Necrosis Factor/immunology , Retrospective Studies , Risk Factors , Transplantation, Homologous/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 9ABSTRACT
T-cell immune response cDNA 7 (TIRC7) is a recently described T-cell costimulatory molecule that exhibits a central role in T-cell activation in vitro and in vivo. The present study was undertaken to investigate association between intragraft and peripheral blood mononuclear cell (PBMC) TIRC7 mRNA levels and cardiac allograft rejection in humans. TIRC7 gene expression levels were determined by a quantitative-competitive reverse transcriptase-polymerase chain reaction (QC-RT-PCR) in endomyocardial biopsies and in PBMC from cardiac transplant recipients. Biopsies collected during rejection or up to 15 days before rejection showed heightened TIRC7 mRNA expression in comparison with biopsies without rejection. All prerejection and rejection biopsies showed TIRC7 mRNA upregulation, while this was present in only 30% of the biopsies without rejection. Regarding TIRC7 mRNA in PBMC, transplant recipients showed lower levels than healthy individuals and, in contrast to the results obtained in biopsies, the levels were lower during rejection than in rejection-free periods. In summary, TIRC7 mRNA expression levels increase in biopsies and decrease in peripheral blood during acute cardiac rejection. We conclude that intragraft detection of TIRC7 transcripts is a useful tool not only for the diagnosis but also for the prediction of acute heart allograft rejection episodes.