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1.
Vox Sang ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39313752

RESUMO

BACKGROUND AND OBJECTIVES: Human platelet antigens (HPA) play a central role in foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura and some cases of platelet therapy refractoriness. The frequency distribution of HPA had not been studied in the Greek population before we started to create a registry of HPA-typed apheresis platelet donors. The aim of this study was the determination of the frequency of various HPA in the Greek population, through the establishment of a registry of typed donors. MATERIALS AND METHODS: Here, we report on the first 1000 platelet donors of Greek origin who gave informed consent and were genotyped for 12 pairs of antithetical HPA by Single Specific Primer-Polymerase Chain Reaction (SSP-PCR), including HPA-1, HPA-3, HPA-5 and HPA-15. Antigen frequencies are reported, and allele frequencies were calculated and compared with other European and non-European populations. Tested donors cover all ABO and Rhesus D antigen spectrum. RESULTS: Antigen and allele frequencies are very similar to other White populations. The frequency of HPA-1bb is 2.9% in our study, and the frequency of HPA-2b, HPA-4b, HPA-9b and HPA-15b is also slightly higher than in other literature reports, while the frequency of HPA-15b was found higher than that of HPA-15a. CONCLUSION: We report antigen and allele frequencies for a large array of clinically significant HPA for the first time in the Greek population. Frequencies are consistent with other European populations. This registry of HPA-typed platelet donors, available to donate on demand, is an important asset for the treatment of FNAIT cases in Greece.

2.
Cell Tissue Bank ; 23(3): 483-488, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34655355

RESUMO

Allogeneic stem cell transplantation (SCT) offers a potential cure for some hematological malignancies. For those patients without a family donor, unrelated donor (MUD) registries serve for identifying the best donor. In the present study, we aimed to give a cross-sectional report of our registry's activity and experience as the first established national MUD registry in the country. The study is retrospective and covers the period of 2016 to 2019. A total of 1855 donor searches were performed, and 642 were included in the study. All data were electronically obtained from the institutional database system. All SCTs were either 10/10 or 9/10 HLA matched and originated from an international registry. The most preferred stem cell source was peripheral blood (70.2%). A quarter of transplants were performed using bone marrow, and cord blood was used with a rate of 1.4%. The pandemic-related problems were similar for the other two national registries. During the pandemic, 71 of 432 patients who were searched for donors underwent stem cell transplant(SCT). The low number was related mostly with postponing of SCTs and/also difficulties in continuing of volunteering and in achievement of stem cells from international registry. During the Covid19 pandemic, the SCT activity of centers decreased according to the national, and international guidelines. The study revealed an organized, and multidirectional capacity of the registry and also the adaptation to unpredicted conditions such as pandemic. On the other hand, there is a need for more effective strategies for donor recruitment and retention programme.


Assuntos
Medula Óssea , COVID-19 , COVID-19/epidemiologia , Estudos Transversais , Documentação , Docentes de Medicina , Humanos , Sistema de Registros , Estudos Retrospectivos , Doadores de Tecidos , Turquia
3.
Int J Immunogenet ; 48(6): 490-495, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34570965

RESUMO

We estimated HLA haplotype frequencies based on individuals homozygous for 4, 5 or 6 loci. Validation of our approach using a sample of over 3.4 million German individuals was successful. Compared to an expectation-maximization algorithm, the errors were larger. However, our approach allows the unequivocal detection of rare haplotypes.


Assuntos
Antígenos HLA , Alelos , Frequência do Gene , Antígenos HLA/genética , Haplótipos/genética , Humanos , Sistema de Registros
4.
Transfus Med Hemother ; 48(4): 228-233, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34539316

RESUMO

INTRODUCTION: The aim of this study was to investigate the allele and genotype frequencies of 8 human platelet antigen (HPA) systems among blood donors from the Blood Transfusion Institute of Serbia and to compare them with published studies. These data would be useful to establish the basis for a platelet apheresis donor registry. MATERIAL AND METHODS: Seventy-two unrelated male platelet apheresis/blood donors from Serbia were typed for 8 HPA systems (HPA-1 to HPA-6, HPA-9, and HPA-15) via the FluoGene method, based on polymerase chain reaction-sequence-specific amplification (PCR-SSP; PCR using sequence-specific primers) with fluorometric signal detection. Allele and genotype frequencies were estimated by direct counting and compared to the expected genotype frequencies according to the Hardy-Weinberg principle. The transfusion mismatch probability was calculated for every HPA specificity. RESULTS: The allele frequencies were: HPA-1a, 0.868; HPA-1b, 0.132; HPA-2a, 0.917; HPA-2b, 0.083; HPA-3a, 0.611; HPA-3b, 0.389; HPA-5a, 0.903; HPA-5b, 0.097; HPA-9a, 0.993; HPA-9b, 0.007; HPA-15a, 0.472; and HPA-15b, 0.528. For HPA-4 and HPA-6 only allele a was detected. DISCUSSION: The HPA allele frequencies of European populations showed no significant differences in comparison with our results. Statistically significant differences were revealed in comparison with some populations of non-European origin. In the tested donors no HPA-2 bb genotype was detected, but we found 1 donor with the rare HPA-9b allele. The biggest transfusion mismatch probability in the Serbian population is for systems HPA-15 (37.4%) and HPA-3 (36.2%), which means that more than a third of random transfusions could cause mismatch in these systems. This study was enabled by the introduction of molecular HPA typing, and it provides initial results of the HPA allele and genotype frequencies in the population of blood donors in Serbia. They will be used to provide a compatible blood supply on demand for treating patients with alloimmune thrombocytopenic disorders. The successful implementation of PCR-SSP with fluorometric signal detection could be further complemented in the future by the introduction of high-throughput methods, which will largely depend on the available financial resources.

5.
Biol Blood Marrow Transplant ; 26(11): 2034-2039, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32712327

RESUMO

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Hematopoietic stem cell transplantation (HCT) is the sole curative therapy for SCD, but few patients will have a matched sibling donor. Patients with SCD are mostly of African origin and thus are less likely to find a matched unrelated donor in international registries. Using HaploStats, we estimated HLA haplotypes for 185 patients with SCD (116 from a Brazilian center and 69 from European Society for Blood and Marrow Transplantation [EBMT] centers) and classified the ethnic origin of haplotypes. Then we assessed the probability of finding an HLA-matched unrelated adult donor (MUD), considering loci A, B, and DRB1 (6/6), in international registries. Most haplotypes were African, but Brazilians showed a greater ethnic admixture than EBMT patients. Nevertheless, the chance of finding at least one 6/6 potential allelic donor was 47% for both groups. Most potential allelic donors were from the US National Marrow Donor Program registry and from the Brazilian REDOME donor registry. Although the probability of finding a donor is higher than previously reported, strategies are needed to improve ethnic diversity in registries. Moreover, predicting the likelihood of having an MUD might influence SCD management.


Assuntos
Anemia Falciforme , Transplante de Células-Tronco Hematopoéticas , Adulto , Anemia Falciforme/genética , Anemia Falciforme/terapia , Brasil , Antígenos HLA/genética , Teste de Histocompatibilidade , Humanos , Sistema de Registros , Doadores de Tecidos , Doadores não Relacionados
6.
Transfus Apher Sci ; 59(4): 102765, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32446634

RESUMO

A clinically significant red cell alloantibody is capable of accelerated destruction of red cells bearing the corresponding antigen. Knowledge of prevalence of these antigens is necessary for performing day to day work and for research in immunohematology. The primary aim of this study was to find the prevalence of 18 clinically significant blood group antigens in blood donors. Secondary objectives were to motivate and create a database of accessible, volunteer O blood group donors and to register rare donors with existing registries. A cross-sectional observational study was conducted in the department of Transfusion Medicine at a large tertiary care hospital in India from October 2016 to May 2018 with a planned sample size of 4800. Study population included healthy blood donors of either gender coming for blood donation to the blood centre. A total of 6678 samples were included in the study. First time donors were 21.41 % while 78.59 % were repeat donors. Voluntary donors constituted 15.81 % while replacement donors were 84.19 %. Male donors were 89.82 % while female donors were 10.18 %. The antigen, phenotype and gene frequencies were calculated. An extended phenotyped voluntary donor database was created and four rare donors were identified. One of these rare donors was registered with the International Rare Donor Panel (IRDP) and rest were registered in a local registry. This study might help enhance the confidence of blood banks in finding appropriate units for patients with unexpected antibodies or with rare phenotypes. It also paves a way for registering rare donors locally and internationally.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Feminino , Humanos , Índia , Masculino , Fenótipo
7.
Int J Immunogenet ; 47(1): 13-23, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31903698

RESUMO

Currently, stem cell donor registries include more than 35 million potential donors worldwide to provide HLA-matched stem cell products for patients in need of an unrelated donor transplant. DKMS is a leading stem cell donor registry with more than 9 million donors from Germany, Poland, the United States, the United Kingdom, India and Chile. DKMS donors have donated hematopoietic stem cells more than 80,000 times. Many aspects of donor registry work are closely related to topics from immunogenetics or population genetics. In this two-part review article, we describe, analyse and discuss these areas of donor registry work by using the example of DKMS. Part 1 of the review gives a general overview on DKMS and includes typical donor registry activities with special focus on the HLA system: high-throughput HLA typing of potential stem cell donors, HLA haplotype frequencies and resulting matching probabilities, and donor file optimization with regard to HLA diversity.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade/métodos , Sistema de Registros , Doadores não Relacionados , Chile , Genética Populacional , Alemanha , Antígenos HLA/genética , Antígenos HLA/imunologia , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunogenética , Índia , Polônia , Reino Unido , Estados Unidos
8.
Int J Immunogenet ; 47(2): 139-148, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32034894

RESUMO

DKMS is a leading stem cell donor registry with more than 9 million donors. Donor registry activities share many touch points with topics from immunogenetics or population genetics. In this two-part review article, we deal with these aspects of donor registry work by using the example of DKMS. In the second part of the review, we focus on donor typing of non-HLA genes, the impact of donor age, gender and CMV serostatus on donation probabilities, the identification of novel HLA, KIR and MIC alleles by high-throughput donor typing, the activities of the Collaborative Biobank and pharmacogenetics in the donor registry context.


Assuntos
Antígenos HLA/genética , Sistema de Registros , Células-Tronco/imunologia , Doadores de Tecidos , Alelos , Tipagem e Reações Cruzadas Sanguíneas , Genótipo , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Imunogenética
9.
Immunogenetics ; 71(10): 589-604, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31741008

RESUMO

The human leukocyte antigen (HLA) is the most polymorphic region in humans. Anthropologists use HLA to trace populations' migration and evolution. However, recent admixture between populations can mask the ancestral haplotype frequency distribution. We present a statistical method based on high-resolution HLA haplotype frequencies to resolve population admixture using a non-negative matrix factorization formalism and validated using haplotype frequencies from 56 world populations. The result is a minimal set of source components (SCs) decoding roughly 90% of the total variance in the studied admixtures. These SCs agree with the geographical distribution, phylogenies, and recent admixture events of the studied groups. With the growing population of multi-ethnic individuals, or individuals that do not report race/ethnic information, the HLA matching process for stem-cell and solid organ transplants is becoming more challenging. The presented algorithm provides a framework that facilitates the breakdown of highly admixed populations into SCs, which can be used to better match the rapidly growing population of multi-ethnic individuals worldwide.


Assuntos
Etnicidade/genética , Antígenos HLA/classificação , Antígenos HLA/genética , Haplótipos , Teste de Histocompatibilidade/métodos , Modelos Genéticos , Frequência do Gene , Genótipo , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Desequilíbrio de Ligação
10.
Transfus Med ; 29(5): 332-337, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31209947

RESUMO

OBJECTIVES: To investigate attrition at the finally selected donor stage among British Bone Marrow Registry (BBMR) donors, all recruited from blood donors. BACKGROUND: The success of searches for unrelated stem cell donors relies on the existence of large international donor registries and the availability of registered donors when matched with a patient. Withdrawal of donors may adversely affect patient outcomes. MATERIALS/METHODS: Data on 2942 planned donations were analysed to assess donor-related deferral rates and associated factors. RESULTS: Overall, 20·2% of requests were cancelled. Transplant centres activated more than half of the cancellations (52·6%). Donor reasons accounted for 46·7% of cancellations (9·4% of requests), of which 61·7% happened for medical and 38·3% for personal reasons. Medical ineligibility of the donor was associated with increasing age (odds ratio [OR] = 1·36, P = 0·011) and peripheral blood stem cell source (OR = 2·22, P = 0·006), and there was some evidence of association with low blood donation reliability (OR = 1·52, P = 0·054). The blood donor reliability score relates to blood donation, and the score worsens if donors consistently fail to attend a donation session when invited. Withdrawal on personal grounds showed associations with donor age (OR = 1·72, P = 0·017, 30-40 years vs other ages), peripheral blood stem cell source (OR = 2·43, P = 0·010) and low blood donor reliability (OR = 1·94, P = 0·007). CONCLUSIONS: To our knowledge, this is the first report on all-cause cancellation at the finally-selected donor stage for international stem cell donor provision, showing 9·4% donor-related cancellation rate. Scores associated with blood donation reliability may be useful to predict stem cell donor withdrawal.


Assuntos
Seleção do Doador , Células-Tronco de Sangue Periférico , Sistema de Registros , Doadores de Tecidos , Adulto , Fatores Etários , Medula Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido
11.
Int J Immunogenet ; 45(6): 337-346, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30188011

RESUMO

The importance of HLA alleles in the process of haematopoietic stem cell transplantation, especially the process of unrelated donor search, is enormous. Macedonian Bone Marrow Donor Registry was established in 2010 and has registered volunteer donors from different nationalities that live in the Republic of Macedonia. The aim of this study was to determine the HLA allele and haplotype frequencies of the volunteer donors from the Macedonian Bone Marrow Donor Registry and to compare this results with the Macedonians from a family study. We analyzed 1,541 donors, with different nationalities, Macedonian, Albanian and Macedonian Muslims that were most numerous in MBMDR, and typed them for HLA-A, -B, -C, -DRB1, whereas Macedonian also for HLA-DQA1 and HLA-DQB1 by SSO method (One Lambda, CA, USA). The most frequent alleles in Macedonians were HLA-A*02, 01, 24; HLA-B*35, 18, 51; HLA-C*07, 04, 12; HLA-DRB1*11, 16, 13; HLA-DQA1*01, 05 and HLA-DQB1*05, 03, 06; in Albanians they were HLA-A*02, 24,01; HLA-B*51, 18, 35; HLA-C*07, 04, 12, HLA-DRB1*11, 13,16; and in Macedonian Muslims they were HLA-A*02, 01, 24; HLA-B*18, 51, 35, HLA-C*07, 04, 02 and HLA-DRB1*11, 16, 14. The most common haplotype in Macedonian was HLA-A*01-B*08-C*07-DRB1*03, whilst in Albanian and Macedonian Muslims HLA-A*02-B*18-C*07-DRB1*11. The comparison of the HLA allele groups between Macedonian from MBMDR and family study showed similar distribution. This study confirmed the close relationship between the populations that live in the Balkan Peninsula.


Assuntos
Antígenos HLA/genética , Haplótipos , Sistema de Registros , Doadores de Tecidos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Macedônia do Norte
12.
Biol Blood Marrow Transplant ; 23(8): 1381-1386, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28396163

RESUMO

HLA haplotype frequencies in a volunteer bone marrow donor registry should reflect the frequencies of potential transplant recipients served by that registry, a challenge in a country with diverse subethnicities of immigrants from Eastern and Western cultures, such as Israel. We evaluated the likelihood of finding suitable donors for hypothetical patients drawn from defined subethnicities in the Ezer Mizion Bone Marrow Donor Registry (EM BMDR) from donors both within and outside the registry now and during the coming decade. On average, bioinformatics modeling predicts that, given current donor recruitment trends, 6/6 high-resolution HLA match rates for Israelis, which currently stand at 40% to 55% for most subethnicities, will rise by up to 1% per year over the next decade. Subethnicities with historically lower rates of interethnic admixture are less likely to find matches outside of their designated group but will benefit from expansion of the registry, whereas ethnically directed drives will enhance matching rates for currently underrepresented subethnicities. Donor searches for the same cohort using a large extramural registry was of only slight benefit for most of the 19 EM BMDR subethnicities evaluated, confirming that local donor registries that reflect the ethnic diversity of the community being served are best equipped to serve the needs of their respective communities. Contemporary trends of an increasingly multiethnic admixture in Israel may impact the effect of ethnic profiling in assessing future match rates for EM BMDR.


Assuntos
Seleção do Doador , Antígenos HLA , Grupos Raciais , Sistema de Registros , Doadores de Tecidos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Biol Blood Marrow Transplant ; 22(4): 759-763, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26724431

RESUMO

Estimation of the National Marrow Donor Program's Be The Match Registry 8/8 (HLA-A, -B, -C, and -DRB1) high-resolution (HR) unrelated donor (URD) match rate was determined in a prior study for each of the 4 most frequent patient race/ethnic groups in the United States: white (WH), Hispanic (HIS), Asian/Pacific Islander (API), and African American (AFA). For patients without an 8/8 HLA-matched URD, a 7/8 match, with a single allele or antigen mismatch, is often accepted by many transplant centers. A follow-up study was designed to determine the 7/8 or better match rate among the 4 major race/ethnic groups, using the same study cohort. Of previously HR tested URDs in the Be The Match Registry, 1344 were randomly selected and treated as pseudo-patients where HR testing was performed to identify a 7/8-matched URD; 98% of WH and over 80% of non-WH race/ethnic groups (HIS, API, and AFA) had at least a 7/8 match identified. In most cases after first testing to identify an 8/8-matched URD, a 7/8-matched URD was identified after typing just 1 URD. Extending criteria to identify a 9/10 match (included HLA-DQB1) showed the 9/10 absolute match rate decreased between 14% and 21% from the 7/8 match rate for the non-WH groups. This study provides a baseline 7/8 and 9/10 or better HLA match rate that can be further supplemented using the additional worldwide URD inventory. URD match rate information can equip centers in clinical planning and the education of patients seeking a life-saving therapy.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/classificação , Transplante de Células-Tronco Hematopoéticas/etnologia , Sistema de Registros , Adulto , Alelos , Feminino , Expressão Gênica , Doença Enxerto-Hospedeiro/etnologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Antígenos HLA/genética , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Raciais , Estudos Retrospectivos , Irmãos , Transplante Homólogo , Doadores não Relacionados
14.
Transfus Med Hemother ; 43(6): 400-406, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27994526

RESUMO

BACKGROUND: Data on blood donor status obtained from general surveys and health interview surveys have been widely used. However, the integrity of data on self-reported blood donor status from surveys may be threatened by sampling and non-sampling error. Our study aimed to compare self-reported blood donors (including one-time as well as regular donors) from the Swiss Health Survey 2012 (SHS) with register-based blood donors recorded by blood establishments and evaluate the direction and magnitude of bias in the SHS. METHODS: We compared population-weighted SHS point estimates of the number of blood donors with their corresponding 95% confidence intervals to the respective figures from blood donor registries (birth cohorts 1978-1993) and estimates of donors based on period donor tables derived from blood donor registries (birth cohorts 1920-1993). RESULTS: In the birth cohorts 1978-1993, the SHS-predicted number of donors was 1.8 times higher than the respective number of donors based on registry data. Adjusting for foreign and naturalized Swiss nationals that immigrated after their 18th birthday, the SHS overall predicted number of donors was 1.6 times higher. Similarly, SHS estimates for the 1920-1993 birth cohorts were 2.4 and 2.1 times higher as compared to register-based estimates. Generally, the differences between SHS and register-based donors were more pronounced in men than in women. CONCLUSION: Self-reported blood donor status in the SHS is biased. Estimates of blood donors are substantially higher than respective estimates based on blood donor registries.

15.
Biol Blood Marrow Transplant ; 21(1): 137-41, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25307419

RESUMO

The National Marrow Donor Program's Be The Match Registry(®) facilitates the worldwide utilization of unrelated donor (URD) grafts for patients in need of a hematopoietic cell transplantation. In this study, we estimate the URD match rate for patients of White (WH), Hispanic (HIS), Asian/Pacific Islander (API), and African American/Black (AFA) race and ethnic groups. We chose 1344 URD at random as "pseudo-patients" (PP) to estimate the likelihood of finding an 8/8 or 10/10 high-resolution HLA-A,-B,-C,-DRB1 (and -DQB1) matched URD. Searches were conducted in the Be The Match Registry database for each PP at 2 time points: 2009 and 2012. URD who were a potential match for a PP by low/intermediate resolution were HLA typed by sequence-based typing to resolve the matching status. The 8/8 match rate for WH PP improved from 68% in 2009 to 72% in 2012. Corresponding match rates were 41% to 44% for HIS, 44% to 46% for API, and 27% to 30% for AFA, for 2009 and 2012, respectively. The 2012 10/10 match rates were 67% for WH, 38% for HIS, 41% for API, and 23% for AFA. These results provide baseline 8/8 and 10/10 match rate estimates by race for patients seeking an URD.


Assuntos
Medula Óssea/metabolismo , Antígenos HLA/genética , Sistema de Registros , Doadores não Relacionados , Povo Asiático , População Negra , Medula Óssea/imunologia , Transplante de Medula Óssea , Bases de Dados Factuais , Expressão Gênica , Antígenos HLA/imunologia , Hispânico ou Latino , Teste de Histocompatibilidade , Humanos , População Branca
16.
Tissue Antigens ; 86(3): 218-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26198733

RESUMO

The allele HLA-DQB1*05:48 differs from HLA-DQB1*05:01:01 by a non-synonymous T to C substitution at nucleotide position 1693 in exon 2.


Assuntos
Alelos , Cadeias beta de HLA-DQ/genética , Sistema de Registros , Células-Tronco/metabolismo , Doadores de Tecidos , Sequência de Bases , Humanos , Dados de Sequência Molecular , Arábia Saudita , Alinhamento de Sequência
17.
Am J Kidney Dis ; 66(1): 23-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25936672

RESUMO

There are more than 325 living kidney donors who have developed end-stage renal disease and have been listed on the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) deceased donor kidney wait list. The OPTN/UNOS database records where these kidney donors are listed and, if they donated after April 1994, where that donation occurred. These 2 locations are often not the same. In this commentary, I examine whether a national living donor registry should be created and whether transplantation centers should be notified when one of their living kidney donors develops end-stage renal disease. I consider and refute 5 potential objections to center notification. I explain that transplantation centers should look back at these cases and input data into a registry to attempt to identify patterns that could improve donor evaluation protocols. Creating a registry and mining the information it contains is, in my view, our moral and professional responsibility to future patients and the transplantation endeavor. As individuals and as a community, we need to acknowledge the many unknown risks of living kidney donation and take responsibility for identifying these risks. We then must share information about these risks, educate prospective donors about them, and attempt to minimize them.


Assuntos
Falência Renal Crônica/epidemiologia , Transplante de Rim , Doadores Vivos , Sistema de Registros , Obtenção de Tecidos e Órgãos , Seleção do Doador/ética , Seleção do Doador/normas , Humanos , Falência Renal Crônica/cirurgia , Doadores Vivos/psicologia , Doadores Vivos/estatística & dados numéricos , Risco , Obtenção de Tecidos e Órgãos/ética , Obtenção de Tecidos e Órgãos/organização & administração , Obtenção de Tecidos e Órgãos/normas , Listas de Espera
18.
Tissue Antigens ; 83(1): 17-26, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24355004

RESUMO

In order to study the impact of human leucocyte antigen (HLA) polymorphism distribution in identifying a matched haematopoietic stem cells unrelated donor (UD), we performed a multi-centric retrospective analysis with the aim of comparing the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 phenotypes of 2126 patients (772 patients for whom a donor search failed to identify a matched UD, and 1354 patients who received a 10/10 allele level matched UD). Our results showed that rare HLA-C is often responsible for difficulty in identifying a donor. This locus may add a degree of complexity to a supposed 'frequent' HLA-A HLA-B and HLA-DRB1 phenotype, turning this phenotype into a less frequent one. For example, 32.5% of the phenotypes in the non-transplanted patients could not be explained by any of the pairs of known HLA-A, HLA-B, HLA-C and HLA-DRB1 haplotypes while this percentage dropped to less than 2% if combinations of only HLA-A, HLA-B and HLA-DRB1 haplotypes were considered. Such situations can be anticipated by computing an index, based on HLA haplotype frequency, the average registry sample size (ARS). ARS is defined as the inverse of the phenotype frequency computed using all corresponding pairs of haplotype frequencies. ARS confirmed that the most significant difference between transplanted and non-transplanted patients was correlated with the introduction of the locus HLA-C in the analysis (median: 8.3e + 4 vs 3.1e + 6, P < 0.0001). The higher the ARS the lower the likelihood of finding a 10/10 match UD reflecting the rareness of the patient's HLA. The area under receiver operator characteristics (AUROC) values of the ARS computation for HLA-A, HLA-B and HLA-DRB1 was 0.82 (0.80; 0.84) at a low-resolution level (two digits). Overall, our study promotes the use of haplotype frequency-based computations to develop computer-assisted donor search.


Assuntos
Simulação por Computador , Seleção do Doador/métodos , Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas , Adulto , Tomada de Decisões Assistida por Computador , Feminino , Frequência do Gene , Antígenos HLA/genética , Histocompatibilidade , Humanos , Masculino , Fenótipo , Probabilidade , Prognóstico , Estudos Retrospectivos , Doadores de Tecidos , Adulto Jovem
19.
Transpl Immunol ; 82: 101985, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38184211

RESUMO

Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Refugiados , Migrantes , Humanos , Etnicidade/genética , Doadores de Tecidos , Antígenos de Histocompatibilidade Classe I/genética , Células-Tronco Hematopoéticas , Frequência do Gene , Antígenos HLA-A/genética , Alelos , Teste de Histocompatibilidade , Haplótipos
20.
Front Genet ; 15: 1375352, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560292

RESUMO

Race, ethnicity, and ancestry are terms that are often misinterpreted and/or used interchangeably. There is lack of consensus in the scientific literature on the definition of these terms and insufficient guidelines on the proper classification, collection, and application of this data in the scientific community. However, defining groups for human populations is crucial for multiple healthcare applications and clinical research. Some examples impacted by population classification include HLA matching for stem-cell or solid organ transplant, identifying disease associations and/or adverse drug reactions, defining social determinants of health, understanding diverse representation in research studies, and identifying potential biases. This article describes aspects of race, ethnicity and ancestry information that impact the stem-cell or solid organ transplantation field with particular focus on HLA data collected from donors and recipients by donor registries or transplant centers.

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