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1.
HLA ; 99(3): 160-166, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34997833

RESUMO

The characterization of the expression profile of HLA questionable alleles (Q) is clinically relevant in allogeneic hematopoietic stem cell transplantation (HSTC) because an aberrant expression of these alleles could lead to transplantation-related complications. HLA-DQB1*03:01:01:21Q shows a substitution at the donor splice site of intron 3 that potentially could affect the expression of this allele. In order to determine their expression profile at RNA and protein level, we analyzed the presence of the HLA-DQ7 molecule by complement-dependent cytotoxicity test (CDC) and flow cytometry, and their RNA processing by cDNA analyses and sequencing by Sanger methods. Our results reveal that HLA-DQ7 is not detectable by serological methods, this is confirmed by cDNA methods demonstrating the absence of specific HLA-DQB1*03:01:01:21Q mRNA, probably due to an intron 3 retention that creates a premature TGA stop codon, leading to mRNA degradation via nonsense-mediated decay (NMD). These findings demonstrate that the HLA-DQB1*03:01:01:21Q allele is nonexpressed, thus it has been renamed as DQB1*03:01:01:21N.


Assuntos
RNA , Alelos , DNA Complementar/genética , Cadeias beta de HLA-DQ/genética , Humanos
2.
Stem Cell Res Ther ; 12(1): 233, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849662

RESUMO

BACKGROUND: iPSC (induced pluripotent stem cells) banks of iPSC lines with homozygous HLA (human leukocyte antigen) haplotypes (haplobanks) are proposed as an affordable and off-the-shelf approach to allogeneic transplantation of iPSC derived cell therapies. Cord blood banks offer an extensive source of HLA-typed cells suitable for reprogramming to iPSC. Several initiatives worldwide have been undertaken to create national and international iPSC haplobanks that match a significant part of a population. METHODS: To create an iPSC haplobank that serves the Spanish population (IPS-PANIA), we have searched the Spanish Bone Marrow Donor Registry (REDMO) to identify the most frequently estimated haplotypes. From the top ten donors identified, we estimated the population coverage using the criteria of zero mismatches in HLA-A, HLA-B, and HLA-DRB1 with different stringencies: high resolution, low resolution, and beneficial mismatch. RESULTS: We have calculated that ten cord blood units from homozygous donors stored at the Spanish cord blood banks can provide HLA-A, HLA-B, and HLA-DRB1 matching for 28.23% of the population. CONCLUSION: We confirm the feasibility of using banked cord blood units to create an iPSC haplobank that will cover a significant percentage of the Spanish and international population for future advanced therapy replacement strategies.


Assuntos
Células-Tronco Pluripotentes Induzidas , Bancos de Sangue , Antígenos HLA/genética , Haplótipos , Humanos , Estudos Prospectivos , Doadores de Tecidos
3.
HLA ; 97(6): 543-544, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33835734

RESUMO

Three new HLA class I alleles were characterized by next generation sequencing.


Assuntos
Antígenos HLA-A , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Antígenos HLA-A/genética , Humanos
5.
HLA ; 93(4): 234-235, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30734534

RESUMO

Three new HLA alleles, HLA-C*05:203, -C*15:10:04 and DRB1*01:99, were characterized in the Spanish population.


Assuntos
Alelos , Éxons , Antígenos HLA-C/genética , Mutação Puntual , Humanos , Espanha
7.
Cell Tissue Bank ; 18(3): 335-341, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28748417

RESUMO

The implementation of nucleic acid testing in donor screening has improved the safety of tissue allografts. Although infectious disease transmission can be considered a rare event, the detection of occult hepatitis B infection remains challenging. The studies concerning this risk are mainly based on testing blood specimens. This work shows the correlation between results of samples obtained from donor blood and the corresponding tissue washing solution. Hepatitis B virus deoxyribonucleic acid was detected both in bone allografts from donors with serological profiles associated to active hepatitis B infection and occult hepatitis B infection. These results suggest that hepatitis B virus seems to concentrate in bone marrow even when a low viral load is present in peripheral blood. Even detection at molecular level is not enough to avoid the risk of hepatitis B virus transmission and a multiparametrical evaluation is required in tissue donor screening. The role of clinicians in recognition and reporting of allograft-associated infections is a major concern for the acquisition of experience to be applied in risk control of disease transmission.


Assuntos
Aloenxertos/virologia , Osso e Ossos/virologia , Seleção do Doador , Vírus da Hepatite B/isolamento & purificação , Hepatite B/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/virologia , Seleção do Doador/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bancos de Tecidos , Carga Viral
8.
Transfusion ; 56(4): 831-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26585542

RESUMO

BACKGROUND: The risk of transfusion-transmitted infection (TTI) has been minimized by introduction of nucleic acid testing (NAT) and pathogen inactivation (PI). This case report describes transmission of human immunodeficiency virus Type 1 (HIV-1) to two recipients despite these measures. STUDY DESIGN AND METHODS: In March 2009 a possible TTI of HIV-1 was identified in a patient that had received pooled buffy coat platelet concentrate (BC-PLT) in November 2005. The subsequent lookback study found two more patients who had received methylene blue (MB)-treated fresh-frozen plasma (FFP) and red blood cells (RBCs) from the same donation. In November 2005 the donor had tested negative for both HIV antibodies and HIV-1 RNA by 44 minipool (44 MP) NAT. Repository samples of this donation and samples from the recipients were used for viral load (VL) and sequence analysis. RESULTS: HIV-1 RNA was detectable by individual donation (ID)-NAT in the repository sample from the 2005 window period donation and a VL of 135 copies/mL was measured. HIV-1 infection was confirmed in both recipients of both BC-PLT (65 mL of plasma) and MB-FFP (261 mL of plasma), but not in the patient that had received 4-week-old RBCs (20 mL of plasma). The sequence analysis revealed a close phylogenetic relationship between the virus strains isolated from the donor and recipients, compatible with TTI. CONCLUSIONS: Approximately 17,600 and 4400 virions in the MB-FFP and BC-PLT were infectious, but 1350 virions in the RBCs were not. ID-NAT would have prevented this transmission, but the combination of MP-NAT and MB-PI did not.


Assuntos
Transfusão de Componentes Sanguíneos/efeitos adversos , Infecções por HIV/transmissão , HIV-1 , Luz , Azul de Metileno/farmacologia , Plasma/virologia , Inativação de Vírus , Adulto , Doadores de Sangue , Infecções por HIV/sangue , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/isolamento & purificação , HIV-1/efeitos da radiação , Humanos , Masculino , Plasma/efeitos dos fármacos , Plasma/efeitos da radiação , RNA Viral/sangue , Falha de Tratamento , Inativação de Vírus/efeitos dos fármacos , Inativação de Vírus/efeitos da radiação , Adulto Jovem
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