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2.
Transplantation ; 105(6): 1317-1325, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34019363

RESUMO

BACKGROUND: In March 2016, Australia's deceased donor kidney allocation program introduced calculated panel reactive antibody (cPRA) based on antibody exclusions using multiplex assays to define sensitization for waitlisted candidates. We aimed to assess the impact of this change and review access to transplantation for highly sensitized patients under the current allocation rules. METHODS: Registry data were used to reconstruct changes in panel reactive antibody (PRA)/cPRA for all patients active on the waiting list between 2013 and 2018. A multilevel, mixed-effects negative binomial regression model was used to determine the association between sensitization and transplantation rate in the cPRA era. RESULTS: Following the introduction of cPRA, there was an increase in the percentage of the waiting list classified as highly sensitized (PRA/cPRA ≥80%) from 7.2% to 27.8% and very highly sensitized (PRA/cPRA ≥99%) from 2.7% to 15.3%. Any degree of sensitization was associated with a decreased rate of transplantation with a marked reduction for those with cPRA 95%-98% (adjusted incidence rate ratio, 0.36 [95% confidence interval, 0.28-0.47], P < 0.001) and cPRA ≥99% (adjusted incidence rate ratio, 0.09 [95% confidence interval, 0.07-0.12], P < 0.001). CONCLUSIONS: The proportion of the waiting list classified as highly sensitized increased substantially following the introduction of cPRA, and despite current prioritization, very highly sensitized patients have markedly reduced access to deceased donor transplantation.


Assuntos
Antígenos HLA/imunologia , Teste de Histocompatibilidade , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim , Doadores de Tecidos/provisão & distribuição , Listas de Espera , Adulto , Austrália , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Acesso aos Serviços de Saúde , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
3.
Clin Transplant ; 35(7): e14336, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33949011

RESUMO

Here the impact of donor specific human leukocyte antigen (HLA) class 2 antibodies (DSA cl 2) on long term outcome after liver transplantation (LT) was investigated. Altogether 156 (44 pediatric and 112 adult) LT recipients were included in the study. Graft fibrosis was assessed by liver elastography and biopsy. DSA cl 2 were determined by Luminex technology. 46% of LT recipients were positive for DSA cl 2 after a median follow-up of 15 years. In the multivariate analysis DSA cl 2 were significantly associated with immunosuppressive monotherapy (OR 5.42; 95% CI: 1.02-28.90; p = .048). Compared to DSA cl 2 negative patients, positive recipients had significantly more graft fibrosis based on the liver stiffness (mean 9.4 ± 9.0 kPa vs. 6.5 ± 6.3 kPa; p < .002) and fibrosis stages determined by liver elastography (p = .016) and the performed liver biopsies (p = .002). Also, a significantly higher incidence of chronic rejections (11% vs. 2%; p = .045) and graft losses (6% vs. 0%; p = .043) were found. In the multivariate regression analysis DSA cl 2 were significantly associated with graft fibrosis (OR 4.57; 95% CI 1.59-13.10; p = .005). So, these data suggest that development of DSA cl 2 occurs more often with immunosuppressive monotherapy and may ultimately result in chronic rejection and graft fibrosis.


Assuntos
Transplante de Fígado , Adulto , Criança , Fibrose , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Antígenos HLA , Teste de Histocompatibilidade , Humanos , Isoanticorpos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos
4.
Medicine (Baltimore) ; 100(21): e25958, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032705

RESUMO

RATIONALE: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been demonstrated to increase the risk of antibody-mediated rejection. We report a case of AT1R-Ab mediated rejection which caused early critical cortical infarction. PATIENT CONCERNS: A 52-year-old man with end-stage kidney disease underwent preemptive kidney transplantation (KT) from his wife. He had no immunologic risk except ABO incompatibility. Proper desensitization treatment were applied prior to KT. On postoperative day 1, he showed stable clinical course with adequate urine output, but there was no decrease in serum creatinine level and imaging studies showed hypoperfusion in the transplanted kidney. DIAGNOSES: Allograft biopsy revealed total cortical infarction with severe necrotizing vasculitis, but the medullary area was preserved. Serum AT1R-Ab concentration was elevated from 10.9 U/mL before KT to 19.1 U/mL on 7 days after KT. INTERVENTIONS: He was treated with plasmapheresis, intravenous immunoglobulin, rituximab, high-dose methylprednisolone, and bortezomib. OUTCOMES: The treatment showed a partial response, and he was discharged with 7.3 mg/dL creatinine level. At 4 months, his creatinine plateaued at 5.5 mg/dL and AT1R-Ab decreased to 3.6 U/mL. LESSONS: This case highlights the risk of early active antibody-mediated rejection by preformed AT1R-Ab, suggesting its ability to exhibit atypical histopathologic findings, such as total cortical infarction.


Assuntos
Rejeição de Enxerto/imunologia , Infarto/imunologia , Isoanticorpos/sangue , Necrose do Córtex Renal/imunologia , Transplante de Rim/efeitos adversos , Receptor Tipo 1 de Angiotensina/imunologia , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Teste de Histocompatibilidade , Humanos , Fatores Imunológicos/administração & dosagem , Infarto/sangue , Infarto/diagnóstico , Infarto/terapia , Isoanticorpos/imunologia , Córtex Renal/irrigação sanguínea , Córtex Renal/imunologia , Córtex Renal/patologia , Necrose do Córtex Renal/sangue , Necrose do Córtex Renal/diagnóstico , Necrose do Córtex Renal/terapia , Falência Renal Crônica/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Plasmaferese , Cônjuges , Fatores de Tempo
5.
Hum Immunol ; 82(8): 568-573, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33910707

RESUMO

HLA antibodies are typically produced after exposure to transplanted tissue, pregnancy, and blood products. Sensitization delays access to transplantation and preclude utilization of donor organs. Infections and vaccinations have also been reported to result in HLA antibody formation. It is not known if patients develop HLA antibodies after infection with SARS-CoV-2. Here we analyzed a series of eighteen patients waiting for kidney transplantation who had symptomatic COVID-19 disease and recovered. None of the patients in this initial series developed de novo HLA antibodies. Notably, there was no increase in preexisting HLA antibodies in four highly sensitized patients with a CPRA > 80%. These preliminary data suggest that there may not be a need to repeat HLA antibody testing or perform a physical crossmatch on admission serum before kidney transplant for COVID-19 recovered patients. Data from a large number of patients with different demographics needed.


Assuntos
COVID-19/imunologia , Antígenos HLA/imunologia , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim , SARS-CoV-2/imunologia , Listas de Espera , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/terapia , COVID-19/virologia , Bases de Dados Factuais , Feminino , Teste de Histocompatibilidade , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/patogenicidade
7.
HLA ; 98(1): 45-46, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33864426

RESUMO

One nucleotide substitution in codon 156 of HLA-A*02:07:01:01 results in a novel allele, HLA-A*02:191.


Assuntos
Antígenos HLA-A , Alelos , Sequência de Bases , Antígenos HLA-A/genética , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA , Taiwan
9.
Transplant Cell Ther ; 27(5): 423.e1-423.e7, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33781751

RESUMO

Finding HLA-matched donors for patients in need of hematopoietic stem cell transplantation (HSCT) stands a better chance in their own ethnic group. This information led many nations to establish unrelated stem cell donor registries. We started our Saudi Stem Cell Donor registry (SSCDR) in 2011. The calculated donor pool size was nearly 1 million donors to find a matched donor for every patient. So far we have recruited 75,145 donors. In this exercise we attempted to investigate the chances of finding a matched donor for Saudi patients in need of HSCT. A total of 445 patients were recruited for this study. Donor searches were carried out locally and internationally using Prometheus software and World Marrow Donor Association Search and Match Service, respectively. Only 24% of the patients found a matched donor in our registry, 12% found a donor in other registries, making it a total of 36% of our patients who have the chance to find a full 10/10 HLA-matched donor. However, when we included 9/10 and 8/10 with the full matched donors, the chances go up to 83%. The top scoring registries for number of patients finding 10/10 matched donors were SSCDR (108), Deutsche Stammzellspenderdatei Nabelschnurblut (n = 52), King Faisal Specialist Hospital & Research Centre Stem Cell Donor Registry (n = 52), NMDP-National Marrow Donor Program/Be The Match (n = 43), TURKOK-Turkish Stem Cell Coordination Centre (n = 39), DKMS United Kingdom (n = 24), and Ezer Mizion Bone Marrow Donor Registry (n = 20). The patient who found the highest number of donors in international registries carried the European haplotype A1-B8-DR3; a total of 272 donors were found, and none of them were from our registry. Patients with the highest matched donor numbers in SSCDR carried haplotypes that were not common in international registries. Having a local registry increases the chances of finding a matched donor for our patients; however, international registries can still add to the chances of finding matched donors. Increasing our donor pool will increase chances of our patients finding a matched donor.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Teste de Histocompatibilidade , Humanos , Arábia Saudita , Reino Unido
10.
HLA ; 97(6): 481-492, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33655664

RESUMO

The human leukocyte antigen (HLA) system plays an important role in hematopoietic stem cell transplantation (HSCT) and organ transplantations, immune disorders as well as oncological immunotherapy. However, HLA typing remains a challenging task due to the high level of polymorphism and homology among HLA genes. Based on the high-throughput next-generation sequencing data, new HLA typing algorithms and software tools were developed. But there is still a deficit of systematic comparative studies to assist in the selection of the optimal analytical approaches under different conditions. Here, we present a detailed comparison of eight software tools for HLA typing on different real datasets (whole-genome sequencing, whole-exome sequencing and transcriptomic sequencing data) and in-silico samples with different sequencing lengths, depths, and error rates. We figure out the algorithms with the best efficiency in different scenarios, and demonstrate the effect of different raw reads on analytical performances. Our results provide a comprehensive picture of specifications and performances of the eight existing HLA genotyping algorithms, which could assist researchers in selecting the most appropriate tool for specific raw datasets.


Assuntos
Antígenos HLA , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Antígenos HLA/genética , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA
11.
HLA ; 97(6): 534-535, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33709621

RESUMO

The novel HLA-A*26:208 allele was characterized using two next generation sequencing technologies.


Assuntos
Antígenos HLA , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Antígenos HLA-A/genética , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA
12.
HLA ; 97(6): 529-530, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33713578

RESUMO

One nucleotide substitution in codon 316 of HLA-A*24:02:01:01 results in a novel allele, HLA-A*24:353.


Assuntos
Antígenos HLA-A , Alelos , Sequência de Bases , Antígenos HLA-A/genética , Haplótipos , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA , Taiwan
13.
HLA ; 97(6): 512-519, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33719220

RESUMO

The International human leukocyte antigen (HLA) and Immunogenetics Workshops (IHIWs) have fostered international collaborations of researchers and experts in the fields of HLA, histocompatibility and immunology. These IHIW collaborations have comprised many projects focused on achieving a variety of specific goals. The international and collaborative nature of these projects necessitates the collection and analysis of complex data generated in multiple laboratories, often using multiple methods of acquisition. Collection and storage of these data in a consistent way adds value to IHIW projects, which can be extended to future work. DNA-based genotyping data, especially HLA genotyping data, can be transmitted in the form of a Histoimmunogenetics Markup Language (HML) document. HML facilitates clear communication of a genotype and supporting metadata, such as, sequencing platform, laboratory assays, consensus sequence, and interpretation. Sequence information can be reported relative to known reference sequences, which add meaning and context to genotypes. Selecting the correct reference sequence for a given allele sequence is nuanced, and guidelines have emerged through collaborative community efforts such as Data Standards Hackathons. Here, we describe the guidelines established for the selection of reference sequences to be used in transmission of HLA (and MICA/MICB) genotyping data for the 18th IHIW.


Assuntos
Antígenos HLA , Imunogenética , Alelos , Genótipo , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe I/genética , Teste de Histocompatibilidade , Humanos
14.
HLA ; 97(6): 555-557, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33743181

RESUMO

One nucleotide substitution in codon 156 of HLA-C*01:02:01:01 results in a novel allele, HLA-C*01:22.


Assuntos
Antígenos HLA-C , Alelos , Sequência de Bases , Antígenos HLA-C/genética , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA , Taiwan
16.
HLA ; 97(6): 552-554, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33755346

RESUMO

Recombination between HLA-B*15:01:01:01 and HLA-B*54:01:01:01, HLA-B*55:02:01:01 or HLA-B*59:01:01:01 resulted the novel allele of HLA-B*15:86.


Assuntos
Genes MHC Classe I , Antígenos HLA-B , Alelos , Sequência de Bases , Antígenos HLA-B/genética , Haplótipos , Teste de Histocompatibilidade , Humanos , Análise de Sequência de DNA , Taiwan
17.
Mol Immunol ; 133: 154-162, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33667985

RESUMO

Identification of anti-human leukocyte antigen (HLA) antibodies (Abs) is based on Luminex™ technology. We used bioinformatics to (i) study the correlations of mean fluorescence intensities (MFIs) for all the possible allele pairs, and (ii) determine the degree of epitope homology between HLA antigens. Using MFI data on anti-HLA Abs from 6000 Luminex™ assays, we provide an updated overview of class I and II HLA antigen cross-reactivity in which each node corresponded to an allele and each link corresponded to a strong correlation between two alleles (Spearman's ρ > 0.8). We compared these correlations with the serological groups and the results of an epitope analysis. The strongest correlations concerned allele-specific Abs directed against the same antigen. For the HLA-A locus, the highest values of Spearman's ρ reflected broad specificity. For the HLA-B locus, graphs defined the HLA-Bw4 public epitope, and correlations between HLA-A and -B alleles were only present for beads with the same Bw4 public epitope. For the HLA-C locus, we identified two groups that differed with regard to their KIR ligand subclassification. Lastly, the HLA-DRB1 subgroups were part of a network. In the epitope analysis, Spearman's ρ was related to the number of matched epitopes within pairs of alleles. The combination of Spearman's ρ with simple, undirected graphing constitutes an effective tool for understanding routinely encountered cross-reactivity profiles. Based on this model, we have implemented an online data visualization tool available at http://cusureau.pythonanywhere.com/.


Assuntos
Especificidade de Anticorpos/imunologia , Epitopos/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/métodos , Isoanticorpos/imunologia , Biologia Computacional/métodos , Reações Cruzadas/imunologia , Humanos , Estudos Retrospectivos
18.
J Immunol Methods ; 492: 112994, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33626382

RESUMO

The annual meeting of the Association of Medical Laboratory Immunologists (AMLI) was convened virtually over the month of August. Prior to the emergence of the COVID-19 pandemic, AMLI's scientific committee had chosen the following topics as the focus of its 2020 meeting: Histocompatibility Testing and Transplant Immunology; Secondary Immunodeficiency and Immunotherapy Monitoring; ANA Update; and Emerging Infectious Diseases and New Algorithms for Testing. Given the central role of the discipline in the evaluation of the host response to infection, it was apt to add a separate session on antibody testing for SARS-CoV-2 infections to the original program. The current report provides an overview of the subjects discussed in the course of this meeting.


Assuntos
Alergia e Imunologia , COVID-19/imunologia , Imunoterapia/métodos , SARS-CoV-2/fisiologia , Sociedades Médicas , Algoritmos , Animais , Processos Grupais , Teste de Histocompatibilidade , Interações Hospedeiro-Patógeno , Humanos , Laboratórios , Pandemias , SARS-CoV-2/química , Imunologia de Transplantes , Realidade Virtual
20.
Am J Hematol ; 96(5): 571-579, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33606297

RESUMO

Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for bone marrow failure or hematopoietic malignant diseases for Fanconi anemia (FA) patients. Although results have improved over the last decades, reaching more than 90% survival when a human leukocyte antigen (HLA)-identical donor is available, alternative HCT donors are still less reported. We compared HCT outcomes using HLA-mismatched unrelated donors (MMUD; n = 123) or haplo-identical donors (HDs), either using only in vivo T cell depletion (n = 33) or T cells depleted in vivo with some type of graft manipulation ex vivo (n = 59) performed for FA between 2000 and 2018. Overall survival (OS) by 24 months was 62% (53-71%) for MMUD, versus 80% (66-95%) for HDs with only in vivo T cell depletion and 60% (47-73%) for HDs with in vivo and ex vivo T cell depletion (p = .22). Event-free survival (EFS) was better for HD-transplanted FA patients with only in vivo T cell depletion 86% (73-99%) than for those transplanted from a MMUD 58% (48-68%) or those with graft manipulation 56% (42-69%) (p = .046). Grade II-IV acute graft-versus-host disease (GVHD) was 41% (MMUD) versus 40% (HDs with no graft manipulation) versus 17% (HDs with T cell depleted graft), (p = .005). No differences were found for the other transplant related outcomes. These data suggest that HDs might be considered as an alternative option for FA patients with better EFS using unmanipulated grafts.


Assuntos
Transplante de Medula Óssea , Anemia de Fanconi/terapia , Antígenos HLA/imunologia , Histocompatibilidade , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Aloenxertos , Transplante de Medula Óssea/estatística & dados numéricos , Criança , Anemia de Fanconi/genética , Anemia de Fanconi/mortalidade , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/genética , Haplótipos , Histocompatibilidade/genética , Histocompatibilidade/imunologia , Teste de Histocompatibilidade , Humanos , Estimativa de Kaplan-Meier , Doadores Vivos , Depleção Linfocítica , Masculino , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Disfunção Primária do Enxerto/epidemiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Irmãos , Subpopulações de Linfócitos T/imunologia , Resultado do Tratamento
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