RESUMEN
We describe a new HLA-A*02 allele, identified in a cord blood unit and in her mother. Nucleotide sequence analysis showed the presence of a new HLA-A*02 allele identical to HLA-A*02010101 except for a non-synonymous nucleotide exchange in exon 4 modifying codon 232 from GAG (Glu) to GAC (Asp). No other human leucocyte antigen class I allele sequenced so far shows this triplet at codon 232. The amino acid exchange affects a position that is part of the membrane proximal domain of class I major histocompatibility complex (MHC), designated alpha 3, and involved in the interaction with CD8 molecule. Using molecular modelling approach, the interactions between different subunits of the native and mutated forms of MHC-I resulted in relevant changes.
Asunto(s)
Alelos , Sangre Fetal/metabolismo , Genes MHC Clase I , Antígenos HLA-A/genética , Mutación , Secuencia de Bases , Codón , Femenino , Antígenos HLA , Humanos , Recién Nacido , Modelos Genéticos , Modelos Moleculares , Datos de Secuencia Molecular , Polimorfismo GenéticoRESUMEN
A new HLA-DRB5 allele, HLA-DRB5*0113, has been identified in an Italian patient during routine HLA typing in order to activate a bone marrow donor search. HLA typing was performed by different molecular biology techniques, and the results showed that the HLA-DRB5*0113 allele differs from HLA-DRB5*010101 allele for three nucleotide substitutions at codons 57 (GAC-->GAT; Asp) and 58 (GCT-->GAG; Ala-->Glu) of exon 2.
Asunto(s)
Trasplante de Médula Ósea/inmunología , Antígenos HLA-DR/genética , Prueba de Histocompatibilidad/métodos , Alanina/química , Alanina/genética , Alelos , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Ácido Glutámico/química , Ácido Glutámico/genética , Cadenas HLA-DRB5 , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , MutaciónRESUMEN
Abstract A new human leucocyte antigen (HLA)-DRB1 allele, HLA-DRB1*1149, has been identified in three members of an Italian family during routine sequence based typing. This new allele differs from HLA-DRB1*110101 only for a single nucleotide substitution at position 113 of exon 2 resulting in an amino acid change from Valine (GTG) to Alanine (GCG) at codon 38.
Asunto(s)
Alelos , Antígenos HLA-DR/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Cadenas HLA-DRB1 , Humanos , Italia , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
In this report, we describe the identification of HLA-A*1112, a novel HLA-A*11 allele found in two Italian families. The new allele was detected during routine HLA typing by a polymerase chain reaction sequence-specific primer and was confirmed by high-resolution sequencing-based typing. The nucleotide sequences of HLA-A*1112 exons 2 and 3 are identical to HLA-A*11011 except for a single nucleotide substitution in codon 90 (GAC-->GCC).
Asunto(s)
Alelos , Antígenos HLA-A/genética , Prueba de Histocompatibilidad , Secuencia de Aminoácidos , Sustitución de Aminoácidos/genética , Secuencia de Bases , Codón/genética , Exones/genética , Salud de la Familia , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/genética , Femenino , Mutación del Sistema de Lectura , Predisposición Genética a la Enfermedad/genética , Antígeno HLA-A11 , Humanos , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple/genética , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
We retrospectively examined 29 renal allograft biopsy specimens from 42 kidney transplant recipients by means of molecular biologic techniques (nested polymerase chain reaction), immunohistochemical analysis (anti-SV40 antibody), and histologic examination to evaluate the presence of polyomaviruses (PVs), viral genotypes, genomic mutations, and their pathologic significance. PV genomes were found in six cases (21%); restriction fragment length polymorphism analysis characterized 4 as JC virus (JCV) and 2 as BK virus (BKV). The latter also were positively stained immunohistochemically and showed histologically typical intranuclear viral inclusions; JCV cases were negative. DNA sequence analysis revealed only minor changes in the 4 JCV cases (3 archetypes and 1 JCV type 3, not associated with a known pathogenic genotype) but identified 2 specific variants in the BKV isolates (AS and WW strains). Given the different histologic findings (mixed inflammatory infiltration in the AS and no inflammation in the WW strain), we speculate that different BKV strains may cause differential damage in transplanted kidneys. Finally, the negative histologic and immunohistochemical JCV results, as well as the absence of viral mutations, indicate that JCV renal infection is latent in transplant recipients.
Asunto(s)
Biopsia con Aguja , ADN Viral/química , Trasplante de Riñón , Riñón/virología , Poliomavirus/genética , Análisis de Secuencia de ADN , Virus BK/genética , Recuento de Linfocito CD4 , Rechazo de Injerto/virología , Humanos , Inmunohistoquímica , Virus JC/genética , Mutación , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Poliomavirus/aislamiento & purificación , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
Three novel Gd chelates containing on their external surface pendant phosphonate and carboxylate groups, which promote the interaction with the positively charged groups of polyornithine and polyarginine, have been synthesized. Their solution structures have been assessed on the basis of 1H- and 31P-NMR spectra of the Eu and Yb analogues. A thorough investigation of the relaxometric (1H and 17O) properties of the Gd chelates has been carried out and the observed relaxivities have been accounted for the sum of three contributions arising from water molecules in the first, second, and outer coordination layers, respectively. It has been found that the occurrence of a tight second coordination coating renders the dissociation of the water molecule directly coordinated to the Gd ion more difficult. The binding interactions between the negatively charged Gd chelates and the positively charged groups of polyornithine (ca. 140 residues) and polyarginine (ca. 204 residues) have been evaluated by means of the proton relaxation enhancement (PRE) method. Although the binding interaction decreases markedly in the presence of competitive anions in the solution medium, the affinity is strong enough that in blood serum it is possible to meet the conditions where most of the chelate is bound to the polyamino acid substrate. On this basis one may envisage a novel route for a MRI location of tumors as it is known that positively charged polyamino acids selectively bind to tumors having a greater negative charge than non-tumor cells.