ABSTRACT
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.
Subject(s)
Alleles , Fetal Blood/metabolism , Genes, MHC Class I , HLA-A Antigens/genetics , Mutation , Base Sequence , Codon , Female , HLA Antigens , Humans , Infant, Newborn , Models, Genetic , Models, Molecular , Molecular Sequence Data , Polymorphism, GeneticABSTRACT
Graft-versus-host disease (GvHD) is the main complication after haematopoietic stem cells transplantation (HSCT) and acute forms (aGvHD) occur in 20-40% of cases even after donor (D) and recipient (R) HLA matching, apparently because of D/R minor histocompatibility antigen (mHA) mismatches and cytokine polymorphisms. The genotype of cytokines and mHA of 77 haematological R following HSCT from HLA identical siblings were determined to detect genetic polymorphisms correlated with GvHD. We analysed TNFA (-863 C/A, -857 C/T and G/A at positions -574, -376, -308, -244, -238), IL-10 (-1082 G/A, -819 C/A, -592 C/T), IL-1B (T/C +3953), IL-1RA (VNTR), HA-1 (H/R allele) and CD-31 (C/G at codon 125, A/G at codon 563). Allele frequencies were in Hardy-Weinberg equilibrium and similar to those of 77 healthy controls. We observed positive correlations between a lower risk of clinically significant aGvHD and both the presence of -1082G -819C -592C IL-10 haplotype when both R and D are considered together and the absence of R IL-1RA allele 2. Furthermore, we observed an association between the absence of TNF-A -238 A allele and the risk of extensive chronic GvHD. mHA and cytokines genotyping would thus seem a valid source of information for the prior identification of recipients with a higher risk of aGvHD.
Subject(s)
Cytokines/genetics , Graft vs Host Disease/genetics , Polymorphism, Single Nucleotide , Adult , Gene Frequency , HLA Antigens/genetics , Haplotypes , Hematologic Diseases/therapy , Hematopoietic Stem Cell Transplantation , Humans , Interleukin-1/genetics , Interleukin-10/genetics , Living Donors , Middle AgedABSTRACT
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.
Subject(s)
Bone Marrow Transplantation/immunology , HLA-DR Antigens/genetics , Histocompatibility Testing/methods , Alanine/chemistry , Alanine/genetics , Alleles , Amino Acid Sequence , Amino Acid Substitution , Base Sequence , Glutamic Acid/chemistry , Glutamic Acid/genetics , HLA-DRB5 Chains , Humans , Male , Middle Aged , Molecular Sequence Data , MutationABSTRACT
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.
Subject(s)
Alleles , HLA-DR Antigens/genetics , Amino Acid Sequence , Amino Acid Substitution , Base Sequence , HLA-DRB1 Chains , Humans , Italy , Molecular Sequence Data , Sequence AlignmentABSTRACT
The FM spectroscopy technique has been applied to two frequency-doubled Nd:YAG lasers to achieve absolute frequency stabilization against the hyperfine structure components of the rovibronic P(54) 32-0 iodine line at 532 nm. A fractional frequency stability of 2 x 10(-13) tau(-1/2) has been obtained for integration times in the range of 1 ms < tau < 10 s. For longer integration times the stability level remains below 10(-13), reaching a minimum value of 4.6 x 10(-14) at 100 s. This high stability level is, to our knowledge, the best value achieved against iodine lines by this locking method and for a fully transportable system.
