RESUMEN
Identification of two novel HLA alleles in Russian bone marrow donors.
Asunto(s)
Alelos , Donantes de Tejidos , Humanos , Federación de Rusia , Antígeno HLA-A2/genética , Antígeno HLA-A2/inmunología , Trasplante de Médula Ósea , Antígeno HLA-B40/genética , Antígeno HLA-B40/inmunología , Exones , Prueba de Histocompatibilidad , Médula Ósea , Análisis de Secuencia de ADNRESUMEN
One nucleotide substitution in codon 140 of HLA-B*40:01:01 results in a novel allele, HLA-B*40:62.
Asunto(s)
Alelos , Codón , Antígeno HLA-B40/genética , Células Madre Hematopoyéticas , Donantes de Tejidos , Pueblo Asiatico , Humanos , TaiwánRESUMEN
The new allele, HLA-B*40:405 differs from B*40:02:01:01 by one nucleotide substitution at codon 304.
Asunto(s)
Alelos , Antígeno HLA-B40/genética , Síndromes Mielodisplásicos/genética , Adulto , Codón , Exones , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , República de CoreaRESUMEN
Full-length sequences of HLA-B*40:01:01, B*40:03 and B*40:40, confirmed by cloning and sequencing in Chinese donors.
Asunto(s)
Alelos , Exones , Antígeno HLA-B40/genética , Polimorfismo Genético , Donantes de Tejidos , Pueblo Asiatico , Secuencia de Bases , Clonación Molecular , Codón/química , Expresión Génica , Antígeno HLA-B40/inmunología , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Intrones , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
To identify HLA alleles closely involved in the autoantigen presentation in acquired aplastic anemia (AA), we studied the HLA allelic loss frequencies of 312 AA patients, including 43 patients with loss of heterozygosity of 6p chromosome (6pLOH). An analysis of the HLA alleles contained in the lost haplotype revealed HLA-B*40:02 to be the most frequently lost allele. When we examined 28 AA (12 6pLOH[+] and 16 6pLOH[-]) patients with HLA-B*40:02 for the presence of leukocytes lacking HLA-B4002 (B4002-) using a new monoclonal antibody specific to this allele, B4002- granulocytes were detected not only in all 6pLOH(+) patients but also in 9 (56%) of the 16 6pLOH(-) patients. Furthermore, 10 (83%) of the 12 6pLOH(+) patients possessed 1.0% to 78% B4002- granulocytes that retained the HLA-A allele on the same haplotype (B4002-A+), suggesting the frequent coexistence of granulocytes that underwent mutations restricted to HLA-B*40:02 with 6pLOH(+) (B4002-A-) granulocytes. Deep sequencing of the HLA-B*40:02 of sorted B4002-A+ granulocytes revealed various somatic mutations, such as frameshift, nonsense, and splice site mutations, in all 15 patients studied. Surprisingly, missense mutations in the α-3 domain of HLA-B*40:02 that are not involved in the antigen presentation were detected exclusively in the B4002+ granulocytes of 3 patients possessing B4002- granulocytes. The markedly high prevalence of leukocytes lacking HLA-B4002 as a result of either 6pLOH or structural gene mutations, or both, suggests that antigen presentation by hematopoietic stem/progenitor cells to cytotoxic T cells via the HLA-B allele plays a critical role in the pathogenesis of AA.
Asunto(s)
Alelos , Anemia Aplásica , Presentación de Antígeno/genética , Autoantígenos , Antígenos HLA-A , Antígeno HLA-B40 , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Aplásica/genética , Anemia Aplásica/inmunología , Anemia Aplásica/patología , Autoantígenos/genética , Autoantígenos/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Femenino , Granulocitos/inmunología , Granulocitos/patología , Antígenos HLA-A/genética , Antígenos HLA-A/inmunología , Antígeno HLA-B40/genética , Antígeno HLA-B40/inmunología , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
HLA-B*40:332 differs from B*40:01:02 by 1 nucleotide difference at nucleotide position 439.
Asunto(s)
Alelos , Exones , Antígeno HLA-B40/genética , Polimorfismo de Nucleótido Simple , Donantes de Tejidos , Sustitución de Aminoácidos , Pueblo Asiatico , Secuencia de Bases , Codón/química , Expresión Génica , Genotipo , Antígeno HLA-B40/inmunología , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Reacción en Cadena de la Polimerasa , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
One nucleotide substitution at codon 254 of HLA-B*40:01:01 results in a new allele, HLA-B*40:329.
Asunto(s)
Alelos , Exones , Antígeno HLA-B40/genética , Mutación Puntual , Donante no Emparentado , Sustitución de Aminoácidos , Secuencia de Bases , Expresión Génica , Genotipo , Antígeno HLA-B40/inmunología , Trasplante de Células Madre Hematopoyéticas , Prueba de Histocompatibilidad , Humanos , Alineación de Secuencia , Análisis de Secuencia de ADN , TaiwánRESUMEN
One nucleotide replacement at residue 147 of HLA-B*40:01:01 results in a new allele, HLA-B*40:01:44.
Asunto(s)
Alelos , Exones , Antígeno HLA-B40/genética , Mutación Puntual , Secuencia de Bases , Trasplante de Médula Ósea , Codón , Genotipo , Antígeno HLA-B40/inmunología , Prueba de Histocompatibilidad , Humanos , Alineación de Secuencia , Análisis de Secuencia de ADN , Taiwán , Donante no EmparentadoRESUMEN
One nucleotide substitution at residue 308 of the HLA-B*40:06:01:01 results in a new allele, HLA-B*40:306.
Asunto(s)
Alelos , Sitios Genéticos , Antígeno HLA-B40/genética , Células Madre Hematopoyéticas/inmunología , Polimorfismo de Nucleótido Simple , Sustitución de Aminoácidos , Secuencia de Bases , Codón , Exones , Expresión Génica , Antígeno HLA-B40/inmunología , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADN , Taiwán , Donante no EmparentadoRESUMEN
The novel HLA-B*40:229 allele shows one nucleotide difference from B*40:02:01 in exon 2 at nucleotide position 97 (C â T).
Asunto(s)
Alelos , Antígeno HLA-B40/genética , Mutación Puntual , Secuencia de Bases , Trasplante de Médula Ósea , China , Codón , Exones , Genotipo , Antígeno HLA-B40/inmunología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Alineación de Secuencia , Análisis de Secuencia de ADN , Donantes de TejidosRESUMEN
HLA-B*58:63 differs from HLA-B*58:01:01 by one nucleotide at position 248 resulting in a single amino acid change.
Asunto(s)
Alelos , Sustitución de Aminoácidos , Antígeno HLA-B40/genética , Polimorfismo de Nucleótido Simple , Pueblo Asiatico , Secuencia de Bases , Trasplante de Médula Ósea , Codón , Exones , Antígeno HLA-B40/clasificación , Antígeno HLA-B40/inmunología , Prueba de Histocompatibilidad , Humanos , Masculino , Datos de Secuencia Molecular , Isoformas de Proteínas/clasificación , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Alineación de Secuencia , Donantes de Tejidos , Adulto JovenRESUMEN
The newly detected HLA-B*40:210 allele has two nucleotide changes in exon 2 compared to B*40:49 allele.
Asunto(s)
Alelos , Sustitución de Aminoácidos , Antígeno HLA-B40/genética , Polimorfismo de Nucleótido Simple , Pueblo Asiatico , Secuencia de Bases , Trasplante de Médula Ósea , Codón , Exones , Antígeno HLA-B40/clasificación , Antígeno HLA-B40/inmunología , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Isoformas de Proteínas/clasificación , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Alineación de Secuencia , Donantes de TejidosRESUMEN
UNLABELLED: Among oncohematological diseases, acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) are characterized by the uncontrolled production and accumulation of blasts that can lead to death. Although the physiopathology of these diseases is multifactorial, a genetic factor seems to be at play. Several studies worldwide have shown association of ALL and AML with several alleles of the major histocompatibility complex (MHC). OBJECTIVE: To determine gene frequencies of HLA-B alleles in Mexicans (individuals with Native American genetic background admixed with European descent) with ALL and AML. METHODS: We compared the HLA-B alleles in 213 patients with ALL and 85 patients with AML to those present in 731 umbilical cord blood (UCB) samples as a control group; this was done by means of the PCR-SSP technique. RESULTS: We found an increased frequency of the HLA-B*40 allele in ALL patients as compared to the control group (14.5% versus 9.84%, P = 0.003, OR = 1.67); this was particularly evident in a subgroup of young (less than 18 years old) ALL patients (P = 0.002, OR = 1.76); likewise, a decreased frequency of HLA-B*40 allele in AML patients was observed as compared to the control group (4.70% versus 9.84%, P = 0.02, OR = 0.42). CONCLUSIONS: These results might suggest opposing effects of the HLA-B*40 in the genetic susceptibility to develop ALL or AML and offer the possibility to study further the molecular mechanisms of cell differentiation within the bone marrow lineage.
Asunto(s)
Genética de Población , Antígeno HLA-B40/genética , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Alelos , Estudios de Casos y Controles , Niño , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Leucemia Mieloide Aguda/patología , Masculino , México , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
Using DNA sequence-based typing method, we found a new HLA-B*40 variant, B*40:221, in a Taiwanese hematopoietic stem cell donor. The allele sequence of B*40:221 is identical to the sequence of B*40:01:01 in exons 2, 3 and 4 except the nucleotides at codon 265 (GGGâAGG). The sequence variation caused one amino acid exchange at residue 265 where Gly was replaced by Arg. The probable HLA-A, -B, -C, -DRB1 and -DQB1 haplotype in association with B*40:221 may be deduced as HLA-A*11:01-B*40:221-C*03:04-DRB1*14:54-DQB1*05:02. The generation of B*40:221 is thought as a result of a nucleotide point mutation involving B*40:01:01. Our discovery of B*40:221 increases the polymorphism of B*40 in Taiwanese.
Asunto(s)
Pueblo Asiatico/genética , Antígeno HLA-B40/genética , Sustitución de Aminoácidos/genética , Secuencia de Bases , Variación Genética , Haplotipos , Células Madre Hematopoyéticas/citología , Prueba de Histocompatibilidad , Humanos , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADN , TaiwánRESUMEN
This new HLA-B allele differs from the closest allele B*40:01:01 by two nucleotide changes at codons 102 and 267.
Asunto(s)
Pueblo Asiatico/genética , Antígeno HLA-B40/genética , Sarcoma Mieloide/genética , Sarcoma Mieloide/inmunología , Adulto , Alelos , Sustitución de Aminoácidos , Secuencia de Bases , China , ADN de Neoplasias/genética , Exones , Femenino , Técnicas de Genotipaje , Prueba de Histocompatibilidad , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Homología de Secuencia de Ácido NucleicoRESUMEN
We detected a rare HLA-B locus allele, B*40:97, in a Taiwanese unrelated donor in our routine HLA SBT (sequence-based typing) exercise for a possible hematopoietic stem cell donation. In exons 2, 3 and 4, the sequence of B*40:97 is identical to the sequence of B*40:02:01 except one nucleotide at nucleotide position 760 (C->T) in exon 4. The nucleotide variation caused one amino acid alteration at residue 230 (L->F). B*40:97 was probably derived from a nucleotide substitution event where C was replaced by T at nucleotide 760 involving B*40:02:01. The HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 haplotype in association with B*40:97 may be deduced as A*26:01-B*40:97-C*03:03-DRB1*11:01-DQB1*03:03. Our recognition of B*40:97 in Taiwanese helps to fill the void of ethnic information for the allele B*40:97 reported to the IMGT/HLA Database.
Asunto(s)
Alelos , Médula Ósea/metabolismo , Antígeno HLA-B40/genética , Donantes de Tejidos , Aminoácidos/genética , Secuencia de Bases , Humanos , Datos de Secuencia Molecular , Nucleótidos/genética , TaiwánRESUMEN
Using a sequence-based typing method, we found a new HLA-B*40 variant, B*40:159, in a Taiwanese hematopoietic stem cell donor. The sequence of B*40:159 is identical to the sequence of B*40:06:01:01 in exons 2 and 3 except the nucleotides at positions 412 (A â G) and 429 (A â C). The sequence variation caused two amino acid exchanges at residue 114 (N â D) and residue 116 (Y â S). The probable HLA-A, HLA-B, HLA-C and HLA-DRB1 haplotype in association with B*40:159 may be deduced as HLA-A*02:06-B*40:159-C*08:01-DRB1*08:03. The generation of B*40:159 is thought as the result of a sequence recombination event where B*46:01:01:01, B*15:01:01 or B*15:02:01 donated a minimum length of the DNA sequence from residue 412 to residue 419 to the recipient sequence of B*40:06:01:01.
Asunto(s)
Alelos , Estudios de Asociación Genética , Antígeno HLA-B40/genética , Haplotipos/genética , Células Madre Hematopoyéticas/metabolismo , Donantes de Tejidos , Secuencia de Aminoácidos , Secuencia de Bases , Antígeno HLA-B40/química , Humanos , Datos de Secuencia Molecular , TaiwánRESUMEN
BACKGROUND: Patients with hematologic malignancies can be successfully treated with donor lymphocyte infusion after HLA-matched allogeneic hematopoietic stem cell transplantation. The effect of donor lymphocyte infusion is mediated by donor T cells recognizing minor histocompatibility antigens. T cells recognizing hematopoietic restricted minor histocompatibility antigens may induce selective graft-versus-leukemia reactivity, whereas broadly-expressed antigens may be targeted in graft-versus-host disease. DESIGN AND METHODS: We analyzed in detail CD8(+) T-cell immunity in a patient with relapsed chronic myelogenous leukemia who responded to donor lymphocyte infusion with minimal graft-versus-host disease of the skin. CD8(+) T-cell clones specific for 4 HLA-B*40:01 restricted minor histocompatibility antigens were isolated which were identified by screening a plasmid cDNA library and whole genome association scanning. Detailed T-cell reactivity and monitoring experiments were performed to estimate the clinical and therapeutic relevance of the novel antigens. RESULTS: Three antigens were demonstrated to be expressed on primary leukemic cells of various origins as well as subtypes of non-malignant hematopoietic cells, whereas one antigen was selectively recognized on malignant hematopoietic cells with antigen presenting cell phenotype. Skin derived fibroblasts were only recognized after pre-treatment with IFN-γ by two T-cell clones. CONCLUSIONS: Our data show evidence for different roles of the HLA-B*40:01 restricted minor histocompatibility antigens in the onset and execution of the anti-tumor response. All antigens may have contributed to a graft-versus-leukemia effect, and one minor histocompatibility antigen (LB-SWAP70-1Q) has specific therapeutic value based on its in vivo immunodominance and strong presentation on leukemic cells of various origins, but absence of expression on cytokine-treated fibroblasts.