ABSTRACT
Three new HLA class I alleles were described in the Spanish population. HLA-A*68:169 and -B*39:129 show one amino acid replacement at the α1-domain, compared to A*68:02 (P47 > L47) and -B*39:06 (S11 > A11), respectively. HLA-B*07:298 presents one nucleotide mutation within exon 1, resulting in a new amino acid position -14, L>Q, which has not been previously described in any HLA protein. Prediction of the B*07:298 signal peptide cleavage did not show significant differences in comparison with that obtained for the rest of HLA-B genes.
Subject(s)
Alleles , Base Sequence , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-B7 Antigen/genetics , Sequence Analysis, DNA , Amino Acid Sequence , HLA-A Antigens/chemistry , HLA-B Antigens/chemistry , HLA-B7 Antigen/chemistry , Haplotypes , Humans , Peptides/chemistryABSTRACT
Three new HLA class I alleles, HLA-A*02:620, HLA-B*27:150 and HLA-B*07:05:01:02, were described in the Spanish Caucasoid population.
Subject(s)
Alleles , HLA-A Antigens/genetics , HLA-B Antigens/genetics , Genes, MHC Class I/immunology , HLA-A Antigens/immunology , HLA-B Antigens/immunology , Humans , Spain , White People/geneticsABSTRACT
A novel HLA-DRB1*13:216 allele was characterized in a Spanish bone marrow donor.
Subject(s)
Alleles , Amino Acid Substitution , Exons , HLA-DRB1 Chains/genetics , Mutation , Base Sequence , Bone Marrow Transplantation , Gene Expression , HLA-DRB1 Chains/immunology , Histocompatibility Testing , Humans , Sequence Analysis, DNA , Spain , Tissue DonorsABSTRACT
An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.
Subject(s)
Donor Selection/methods , Hematopoietic Stem Cell Transplantation/methods , Receptors, KIR/genetics , Gene Frequency , Genotype , Humans , Killer Cells, Natural/immunology , Polymerase Chain Reaction/methods , Polymorphism, Genetic , Quality ControlABSTRACT
In this report we describe a case of somatic mutation in the HLA-B gene in the tumour cells of a patient with acute myelogenous leukaemia (AML). Routine human leukocyte antigen (HLA) typing of patient by serology and molecular methodologies rendered discrepant results regarding the expression of a B*15:01 antigen. Sequencing-based typing of a patient's sample including a very high percentage of blast cells revealed the presence of one nucleotide insertion at exon 3, position 440, codon 123. This insertion resulted in a reading frame shift and a premature stop codon at position 152. The mutation was absent in a sample obtained when the patient was in remission. This case report points out the relevance of the sample source for HLA typing in patients with haematological malignancies.
Subject(s)
Alleles , Exons , Frameshift Mutation , HLA-B15 Antigen/genetics , Leukemia, Myeloid, Acute/genetics , Base Sequence , Codon, Nonsense , Female , Gene Expression , Genotype , HLA-B15 Antigen/immunology , Histocompatibility Testing , Humans , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/pathology , Middle Aged , Sequence Alignment , Sequence Analysis, DNAABSTRACT
Characterization of a novel HLA-B null allele, B*15:375N, with a seven base pair deletion in exon 3.
Subject(s)
Alleles , Base Sequence , Exons , HLA-B Antigens/genetics , Sequence Deletion , HumansABSTRACT
Three novel HLA class II alleles, DRB1*08:70, DQA1*01:13 and DQA1*03:01:03, were characterized.
Subject(s)
Alleles , Histocompatibility Antigens Class II/genetics , Amino Acid Sequence , Exons , HLA-DQ alpha-Chains/chemistry , HLA-DQ alpha-Chains/genetics , HLA-DRB1 Chains/chemistry , HLA-DRB1 Chains/genetics , Histocompatibility Antigens Class II/chemistry , Humans , Lymphoma, Non-Hodgkin/genetics , Sequence Analysis, DNAABSTRACT
The new HLA-DPB1*142:01 allele differs from DPB1*26:01:02 and DPB1*56:01 at codons 65 (I65>L65) and 35 (F35>Y35), respectively.
Subject(s)
Alleles , Graft Rejection , HLA-DP beta-Chains/genetics , Kidney Transplantation , Polymorphism, Single Nucleotide , Base Sequence , Codon , Exons , Fatal Outcome , Histocompatibility Testing , Humans , Molecular Sequence Data , Peru , Sequence Alignment , Sequence Analysis, DNA , Tissue DonorsABSTRACT
HLA-B*51:153 shows two nucleotide differences compared with B*51:08 at codon 163 (CTG>ACG).
Subject(s)
Alleles , HLA-B Antigens/genetics , Point Mutation , Base Sequence , Exons , HLA-B Antigens/immunology , Haplotypes , Histocompatibility Testing , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNA , SpainABSTRACT
HLA-B*49:24 shows one nucleotide difference regarding B*49:10 at codon 12 (ATG>GTG). DRB1*03:64 differs from DRB1*03:01:01 in one amino acid residue at position 59, E>Q.
Subject(s)
Alleles , HLA-B Antigens/genetics , HLA-DRB1 Chains/genetics , Sequence Analysis, DNA , Amino Acid Sequence , HLA-B Antigens/chemistry , HLA-DRB1 Chains/chemistry , Humans , Molecular Sequence Data , Protein Structure, TertiaryABSTRACT
B*08:79 is composed by partial B*08:01:01 and B*07:06 sequences because of a possible recombination event within intron 2.
Subject(s)
Alleles , Exons/genetics , Genome, Human/genetics , HLA-B7 Antigen/genetics , HLA-B8 Antigen/genetics , Recombination, Genetic/genetics , Base Sequence , Humans , Molecular Sequence DataABSTRACT
The novel HLA-B*44:130 allele was found in a Spanish donor. B*44:130 differs from B*44:40 by four nucleotide changes at codons 11, 12 and 24, producing three amino acid replacements, 11A>S, 12M>V and 24T>S.
Subject(s)
HLA-B Antigens/genetics , Alleles , Base Sequence , Codon , Genotype , Humans , Molecular Sequence Data , White PeopleABSTRACT
The new HLA-C allele C*07:170 differs from C*07:01:01 by two nucleotides at exon 3.
Subject(s)
HLA-C Antigens/genetics , Polymorphism, Single Nucleotide , Alleles , Amino Acid Sequence/genetics , Amino Acid Substitution , Histocompatibility Testing , Humans , Molecular Sequence Data , Sequence Homology, Amino AcidABSTRACT
Human leukocyte antigen (HLA) class I sequence-based typing (SBT) for hematopoietic unrelated donor searching in a Romanian Caucasian patient showed the presence of a novel HLA-B allele defined as B*0777. HLA-B*0777 has two nucleotides changes at the same codon from B*0707, resulting an amino acid replacement 99Y > 99S.
Subject(s)
Alleles , HLA-B Antigens/genetics , Amino Acid Sequence , Amino Acid Substitution , Binding Sites , Humans , Molecular Sequence Data , Sequence AlignmentABSTRACT
The association between human leukocyte antigen (HLA) class II antigens and celiac disease (CD) was analyzed in a Spanish population. No association with DRB1*04 and DQB1*0302 was noted. The main associated haplotype (70.8%) was DRB1*03-DQB1*0201-DQA1*0501(DR3-DQ2), followed by DRB1*07-DQB1*0202-DQA1*0201 (DR7-DQ2) haplotype, which is associated with DRB1*11-DQB1*0301-DQA1*0505 (DR11-DQ7). The combinations of DR3-DQ2 with DR7-DQ2, and DR7-DQ2 with DR11-DQ7, present a twofold risk compared with each haplotype in homozygosis. An independence test in DR3-DQ2 haplotype found that association with CD was attributable to the whole haplotype, but for DR7-DQ2 was secondary to DQB1/DQA1. There is no need of a double gene dosage to increase the risk. CD-associated alleles typing demonstrates a very high negative predictive value to exclude CD in risk groups.
Subject(s)
Alleles , HLA-D Antigens/genetics , Haplotypes/genetics , Celiac Disease/genetics , Genetic Predisposition to Disease , Genotype , Humans , Population Groups , SpainABSTRACT
The objective of this study was to analyze the proliferative response of BALB/cmice lymphocytes after in vitro irradiation (0.05 to 6 Gy). The capability of irradiatedlymphocytes for proliferating without any stimulation and after activation withspecific T and B cell mitogens has been evaluated. The results show that ionizingradiation significantly inhibits spontaneous cellular proliferation and that induced bymitogens and that variations in the degree of inhibition are found depending on theinducing proliferation mitogens and the dosage applied. The conclusion drawn is thatdifferent lymphocyte populations have different radiosensitivities, being B cells moresensitive to ionizing irradiation than T cells. Besides, the effects of gamma-irradiationvary according to the different subpopulations of T cells or, alternatively, to differentT-dependent activation mechanisms (AU)
No disponible
Subject(s)
Animals , Male , Mice , Female , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/cytology , Cell Proliferation , T-Lymphocyte Subsets/immunology , Concanavalin A/administration & dosage , Dose-Response Relationship, Immunologic , Lipopolysaccharides/administration & dosage , Mitogens/immunology , Phytohemagglutinins/administration & dosage , Radiation Tolerance , B-Lymphocyte Subsets , Gamma Rays , Dose-Response Relationship, Radiation , Mitogens/administration & dosage , Cell Proliferation/radiation effects , B-Lymphocyte Subsets/radiation effects , T-Lymphocyte Subsets , T-Lymphocyte Subsets/radiation effects , Cells, Cultured , Lymphocyte ActivationABSTRACT
The objective of this study was to analyze the proliferative response of BALB/c mice lymphocytes after in vitro irradiation (0.05 to 6 Gy). The capability of irradiated lymphocytes for proliferating without any stimulation and after activation with specific T and B cell mitogens has been evaluated. The results show that ionizing radiation significantly inhibits spontaneous cellular proliferation and that induced by mitogens and that variations in the degree of inhibition are found depending on the inducing proliferation mitogens and the dosage applied. The conclusion drawn is that different lymphocyte populations have different radiosensitivities, being B cells more sensitive to ionizing irradiation than T cells. Besides, the effects of gamma-irradiation vary according to the different subpopulations of T cells or, alternatively, to different T-dependent activation mechanisms.
Subject(s)
B-Lymphocyte Subsets/immunology , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Gamma Rays , Mitogens/administration & dosage , T-Lymphocyte Subsets/immunology , Animals , B-Lymphocyte Subsets/cytology , B-Lymphocyte Subsets/drug effects , B-Lymphocyte Subsets/radiation effects , Cells, Cultured , Concanavalin A/administration & dosage , Dose-Response Relationship, Immunologic , Dose-Response Relationship, Radiation , Female , Lipopolysaccharides/administration & dosage , Lymphocyte Activation/drug effects , Lymphocyte Activation/radiation effects , Male , Mice , Mice, Inbred BALB C , Mitogens/immunology , Phytohemagglutinins/administration & dosage , Pokeweed Mitogens/administration & dosage , Radiation Tolerance/immunology , T-Lymphocyte Subsets/cytology , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/radiation effectsABSTRACT
Genetic predisposition to celiac disease (CD) is determined primarily by the human leukocyte antigen (HLA) genes (CELIAC1 region; 6p21), although many loci are involved in disease susceptibility. First, we have analysed a large series of CD patients from the Spanish Mediterranean region who had previously been characterised for the HLA complex. We have investigated how relevant regions contribute to CD susceptibility: CELIAC3 (CD28/CTLA4/ICOS region on 2q33) and CELIAC4 (19p13) as well as the tumour necrosis factor alpha (TNF-alpha) and the linfotoxin loci by case-control and association analyses. We highlight the association with the +49*A allele of cytotoxic T-lymphocyte-associated antigen 4 locus (P = 0.01), and the -308*A of TNF-alpha locus (P = 0.0008) in DQ2 individuals, although an independent role for TNF-alpha as risk factor has not been proven. Moreover, we do not confirm the association with the CELIAC4 region polymorphisms described in other populations.
Subject(s)
Antigens, CD/genetics , Antigens, Differentiation/genetics , Celiac Disease/genetics , Genetic Predisposition to Disease , Myosins/genetics , Alleles , CTLA-4 Antigen , Case-Control Studies , Celiac Disease/metabolism , Female , Genotype , Haplotypes , Humans , Male , Polymorphism, Genetic , Spain , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
BACKGROUND: The association of melanoma with HLA class II loci is under extensive debate. Different investigators have found discrepant results due to, at least in part, sample size, patient series heterogeneity, choice of control population and differences in the techniques employed for the detection of HLA antigens and alleles. OBJECTIVES: This study was designed to analyse the possible association of melanoma with HLA class II loci with regard to different clinic pathological factors and to investigate other risk factors for melanoma susceptibility, such as HLA homozygosity. PATIENTS AND METHODS: HLA-DRB1, -DQA1 and -DQB1 genotyping was performed for 117 eastern Spanish patients presenting with primary melanoma. RESULTS: Although there were no significant alterations in the phenotypic frequencies of HLA-DQA1, -DQB1 or -DRB1 alleles in any subgroup of patients when compared with controls, patients exhibited a statistically significant increase in HLA-DQA1 homozygosity rate. This DQA1 homozygosity-specific association was particularly dependent on some features in melanoma patients such as light hair colour, skin type I or II, early age at diagnosis, absence of atypical naevi, or abscence of atypical naevus syndrome phenotype (aetiological fractions about 10-20%). Analysis of homozygosity for single DQA1 alleles showed an increased homozygosity rate for DQA1*0505 and DQA1*0301 in comparison with controls. These DQA1 alleles are in strong linkage disequilibrium with DQB1*0301 in white populations, and DQB1*0301 homozygous individuals were significantly increased in red in or fair-haired patients (relative risk 5.65). CONCLUSIONS: Our results indicate that the contribution of HLA class II alleles to primary melanoma incidence is not significant in the Spanish population. However, homozygosity for the HLA-DQA1 locus (and, perhaps, for the HLA-DQB1*0301 allele) might be considered a potential risk factor for developing melanoma depending on the person's genetic background and, perhaps, on certain environmental conditions.