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B E Shaw,
N P Mayor,
N H Russell,
J F Apperley,
R E Clark,
J Cornish,
P Darbyshire,
M E Ethell,
J M Goldman, A-M Little,
S Mackinnon,
D I Marks,
A Pagliuca,
K Thomson,
S G E Marsh,
J A Madrigal
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ABSTRACT: Disease stage and recipient/donor human leukocyte antigen (HLA) matching are important determinants of outcome in transplantation using volunteer-unrelated donors (VUD). Matching for HLA-A, -B, -C, -DRB1, -DQB1 is beneficial, whereas the importance of DPB1 matching is more controversial. The impact of HLA matching status may differ dependent on disease stage. We investigated the outcome according to the degree of HLA matching at 6 loci, in 488 recipients of predominantly T-cell depleted bone marrow VUD transplants for leukaemia. Survival was significantly better in 12/12-matched transplants in those with early leukaemia (5 years: 63 versus 41% in 10/10 matched, P=0.006), but not late stage disease. Conversely, within the HLA-mismatched group (< or =9/10), there was a significant survival advantage to DPB1 mismatching (5 years: 39 versus 21% in DPB1 matched, P=0.008), particularly in late leukaemia (P=0.01), persisting in multivariate analysis (odds ratio 0.478; 95% confidence interval 0.30, 0.75; P=0.001). These novel findings suggest that the best outcome for patients with early leukaemia, with a 10/10-matched donor, is achieved by matching for DPB1. Conversely, our results suggest that in patients receiving an HLA-mismatched graft, the outcome is significantly better if they are also mismatched for DPB1. We recommend validation of these results in independent datasets.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 11/2009; 24(1):58-65. · 8.30 Impact Factor
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Bone marrow transplantation 02/2009; 44(2):129-30. · 3.00 Impact Factor
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ABSTRACT: We report the identification of two novel major histocompatibility complex (MHC) class I-related chain A (MICA) alleles. MICA*054 has a nucleotide substitution of A to G at position 871 (codon 268), encoding an amino acid change of serine to glycine in the alpha-3 domain. MICA*056 has a nucleotide substitution at position 758 of G to C resulting in the substitution of tryptophan for serine at codon 230, also in the alpha-3 domain.
Tissue Antigens 02/2009; 73(1):85-7. · 2.59 Impact Factor
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ABSTRACT: Registries of volunteer unrelated haematopoietic stem cell donors must make decisions on the procedures used to human leukocyte antigen type new donors based on various factors including available finances and donor diversity. This manuscript describes a comparison of new donor typing strategies for three European registries which was presented for discussion at the 14th International Histocompatibility Workshop.
Tissue Antigens 05/2007; 69 Suppl 1:8-9. · 2.59 Impact Factor
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ABSTRACT: Human leukocyte antigen (HLA) typing of a newly recruited, potential volunteer haematopoietic stem cell donor (ALSM4092AN) indicated the presence of a variant DRB1*13 allele, which has now been named DRB1*1371.
Tissue Antigens 04/2007; 69(3):284-5. · 2.59 Impact Factor
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Tissue Antigens 03/2007; 69(2):200-1. · 2.59 Impact Factor
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J E García-Ortiz,
L Sandoval-Ramírez,
H Rangel-Villalobos,
H Maldonado-Torres,
S Cox,
C A García-Sepúlveda,
L E Figuera,
S G E Marsh, A M Little,
J A Madrigal,
J Moscoso,
A Arnaiz-Villena,
J R Argüello
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ABSTRACT: We describe for the first time the high-resolution profiling of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand-mediated conformational analysis in this population were for class I: HLA-A*240201, *020101/09, *0206, *310102, *680102; HLA-B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA-Cw*0304, *0801, *0102, *040101; and for class II: HLA-DRB1*080201, *1402, *040701; HLA-DQB1*0402, *0301, *0302/07; HLA-DPB1*0402, *0401, *020102. In addition, a novel allele, HLA-A*0257, was found. Based on comparison of presently known HLA-DRB1 and -DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes.
Tissue Antigens 09/2006; 68(2):135-46. · 2.59 Impact Factor
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ABSTRACT: We report here the full-length sequence of a novel HLA-A*0301 allele, A*03010103, which differs from A*03010101 by a single nucleotide substitution (G>T) at position 492 within intron 2. The variant was originally identified by Reference Strand-mediated Conformational Analysis (RSCA) and was confirmed by cloning and sequencing. The difference in RSCA mobility between A*03010101 and A*03010103 demonstrates the sensitivity of RSCA to detect single nucleotide polymorphisms.
Tissue Antigens 02/2005; 65(1):107-9. · 2.59 Impact Factor
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ABSTRACT: A novel human leucocyte antigen-A*02 (HLA-A*02) allele was detected by reference strand-mediated conformation analysis (RSCA) of a DNA sample from a Tarahumara individual. Direct sequencing of HLA-A locus polymerase chain reaction products identified a mutation in one of the alleles. Cloning and sequencing confirmed the presence of a new allele, A*0257 which differed from A*0206 by two nucleotides at positions 355 and 362, inducing changes in residues 95 and 97, respectively, within the peptide-binding site. Those changes suggest that allele A*0257 may have resulted from an intralocus recombination event.
Tissue Antigens 02/2004; 63(1):85-7. · 2.59 Impact Factor
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ABSTRACT: A novel human leucocyte antigen-A*02 (HLA-A*02) allele was detected by reference strand-mediated conformation analysis (RSCA) of a DNA sample from a Tarahumara individual. Direct sequencing of HLA-A locus polymerase chain reaction products identified a mutation in one of the alleles. Cloning and sequencing confirmed the presence of a new allele, A*0257 which differed from A*0206 by two nucleotides at positions 355 and 362, inducing changes in residues 95 and 97, respectively, within the peptide-binding site. Those changes suggest that allele A*0257 may have resulted from an intralocus recombination event.
Tissue Antigens 12/2003; 63(1):85 - 87. · 2.59 Impact Factor
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J Crowley,
R Hagan,
D Clancy,
G Rooney,
C Dunne,
E Lawlor,
P Hayden, A-M Little,
B Soteriou,
S G E Marsh,
J A Madrigal
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ABSTRACT: HLA class II typing by sequence specific oligonucleotide probes (SSOP) on the family of a Burkit's Lymphoma patient produced hybridization patterns indicating the presence of two DRB1, and two linked DQB1 genes on the same maternal chromosome. DRB and DQB1 exon 2 amplification products associated with the novel maternal haplotype were identified by DNA typing techniques: These products corresponded to DRB1*0101, DRB1*1501, DRB5*01, DQB1*0501 and DQB1*0602 alleles. These alleles were seen to co-segregate among siblings sharing the same maternal haplotype. The patient, his mother and two of his siblings each appeared to possess elements of three DRB1, DQA1 and DQB1 genes. HLA DNA typing results indicated that a DNA sequence of approximately 100 Kb, spanning the region between, and including, DRB1 and DQB1 genes was inserted into the maternal haplotype. Serological typing on EBV transformed B lymphocytes obtained from the patient's mother showed three expressed DRB1 antigens. Serology on EBV transformed patient's cells also indicated multiple DRB1 antigen expression. The expression of three DRB1 and DQB1 genes on the cells of this patient would make it virtually impossible to obtain a suitably matched unrelated stem cell donor.
Tissue Antigens 07/2003; 61(6):487-91. · 2.59 Impact Factor
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ABSTRACT: Currently most available† HLA-A, -B and -C DNA sequences cover exons 2 and 3 with a limited number extending to include other exons and introns. We have developed a method for the accurate determination of full-length genomic DNA sequences for HLA-A, -B and -C alleles. The method involves cloning of PCR amplified full-length HLA genes to separate alleles at heterozygous loci. The approach avoids any ambiguities from sequencing heterozygous PCR products directly and also avoids ambiguities from sequencing overlapping PCR products to achieve full-length sequence. To date we have sequenced full-length genomic sequences from representatives of all the major HLA-B and -C allele groups.
Tissue Antigens 03/2003; 61(1):20 - 48. · 2.59 Impact Factor
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ABSTRACT: Currently most available HLA-A, -B and -C DNA sequences cover exons 2 and 3 with a limited number extending to include other exons and introns. We have developed a method for the accurate determination of full-length genomic DNA sequences for HLA-A, -B and -C alleles. The method involves cloning of PCR amplified full-length HLA genes to separate alleles at heterozygous loci. The approach avoids any ambiguities from sequencing heterozygous PCR products directly and also avoids ambiguities from sequencing overlapping PCR products to achieve full-length sequence. To date we have sequenced full-length genomic sequences from representatives of all the major HLA-B and -C allele groups.
Tissue Antigens 02/2003; 61(1):20-48. · 2.59 Impact Factor
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C. Dunne, A.M. Little,
S.T. Cox,
D. Masson,
J. Crowley,
T. Barnes,
S.G.E. Marsh,
G. Rooney,
R. Hagan,
E. Lawlor,
J.A. Madrigal
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ABSTRACT: We report the definition of an HLA class I null allele that has been identified within the B35 group by a combination of serological and molecular typing. This allele, which has been named B*3540N, was detected in a French, potential unrelated hematopoietic stem cell donor of unknown ethnic origin, selected as a probable match for an Irish patient. The presence of the null allele was initially determined by the absence of B35 reactivity by serological typing, in contrast to positive reactions by PCR-SSP and PCR-SSO typing. Subsequent sequencing of clones containing the full genomic sequence of the B*35 allele identified a single nucleotide deletion within exon 4 which resulted in the introduction of a stop codon downstream within exon 4.
Tissue Antigens 09/2002; 59(6):522 - 524. · 2.59 Impact Factor
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C Dunne, A M Little,
S T Cox,
D Masson,
J Crowley,
T Barnes,
S G E Marsh,
G Rooney,
R Hagan,
E Lawlor,
J A Madrigal
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ABSTRACT: We report the definition of an HLA class I null allele that has been identified within the B35 group by a combination of serological and molecular typing. This allele, which has been named B*3540N, was detected in a French, potential unrelated hematopoietic stem cell donor of unknown ethnic origin, selected as a probable match for an Irish patient. The presence of the null allele was initially determined by the absence of B35 reactivity by serological typing, in contrast to positive reactions by PCR-SSP and PCR-SSO typing. Subsequent sequencing of clones containing the full genomic sequence of the B*35 allele identified a single nucleotide deletion within exon 4 which resulted in the introduction of a stop codon downstream within exon 4.
Tissue Antigens 07/2002; 59(6):522-4. · 2.59 Impact Factor
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ABSTRACT: A novel polymorphism was identified in a B*15 allele. B*1566 possesses a nucleotide substitution of C to G at nucleotide 272. This polymorphism encodes an amino acid difference from serine in B*1501101 to cysteine in B*1566 at residue 67. Residue 67 is a constituent of the B pocket and is situated on the alpha1 helix facing into the groove. This mutation may have arisen through interallelic recombination as it has been seen in other B*15 alleles and is also present in most B*14, B*27, B*38, B*39 alleles and in B*7301.
Tissue Antigens 06/2002; 59(5):424-5. · 2.59 Impact Factor
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ABSTRACT: Two new HLA-C alleles have been identified by reverse line blot assay and direct sequencing of polymerase chain reaction (PCR) products. The first polymorphism encodes an amino acid change from lysine in Cw*12022 to asparagine in Cw*1208 at residue 66. The second polymorphism encodes two amino acid changes from isoleucine in Cw*03031 to threonine in Cw*0313 at residue 93 and isoleucine to leucine at residue 94. The functional significance of these polymorphisms on peptide-binding and/or T-cell recognition is unknown.
Tissue Antigens 02/2002; 59(1):49-51. · 2.59 Impact Factor
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ABSTRACT: A novel polymorphism was identified in a B*07 allele. B*0722 possesses a unique nucleotide substitution at nucleotide 481. This polymorphism encodes an amino acid difference from aspartic acid in B*07021 to asparagine in B*0722. The functional significance of this polymorphism on peptide binding and/or T-cell recognition is unknown.
Tissue Antigens 03/2001; 57(2):167-8. · 2.59 Impact Factor
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Immunogenetics 03/2001; 53(1):43-4. · 2.93 Impact Factor
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ABSTRACT: Human leukocyte antigen (HLA) class I polymorphism was studied within a population of 70 unrelated Kolla Amerindians from the far northwest of Argentina close to the Bolivian border. The results indicate that the HLA-A, -B, and -C alleles typical of other Amerindian populations also predominate in the Kolla. These alleles belong to the following allele groups: HLA-A*02, *68, *31, *24, HLA-B*35, *15, *51, *39, *40, *48, and Cw*01, *03, *04, *07, *08, and *15. For the HLA-A locus, heterogeneity was seen for HLA-A*02 with A*0201, *0211, and *0222; and for A*68 with *68012 and *6817, the latter being a novel allele identified in this population. Analysis of HLA-B identified heterogeneity for all Amerindian allele groups except HLA-B*48, including the identification of the novel B*5113 allele. For HLA-C heterogeneity was identified within the Cw*07, *04, and *08 groups with Cw*0701/06, *0702, *04011, *0404, *0803, and *0809 identified. The most frequent "probable" haplotype found in this population was B*3505-Cw*04011. This study supports previous studies, which demonstrate increased diversity at HLA-B compared with HLA-A and -C. The polymorphism identified within the Kolla HLA-A, -B, and -C alleles supports the hypothesis that HLA evolution is subject to positive selection for diversity within the peptide binding site.
Human Immunology 03/2001; 62(2):170-9. · 2.84 Impact Factor
