RESUMEN
To mitigate methane emission from urban natural gas distribution systems, it is crucial to understand local leak rates and occurrence rates. To explore urban methane emissions in cities outside the U.S., where significant emissions were found previously, mobile measurements were performed in 12 cities across eight countries. The surveyed cities range from medium size, like Groningen, NL, to large size, like Toronto, CA, and London, UK. Furthermore, this survey spanned across European regions from Barcelona, ES, to Bucharest, RO. The joint analysis of all data allows us to focus on general emission behavior for cities with different infrastructure and environmental conditions. We find that all cities have a spectrum of small, medium, and large methane sources in their domain. The emission rates found follow a heavy-tailed distribution, and the top 10% of emitters account for 60-80% of total emissions, which implies that strategic repair planning could help reduce emissions quickly. Furthermore, we compare our findings with inventory estimates for urban natural gas-related methane emissions from this sector in Europe. While cities with larger reported emissions were found to generally also have larger observed emissions, we find clear discrepancies between observation-based and inventory-based emission estimates for our 12 cities.
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Contaminantes Atmosféricos , Gas Natural , Ciudades , Gas Natural/análisis , Metano/análisis , Contaminantes Atmosféricos/análisis , LondresRESUMEN
The accuracy of human leukocyte antigen (HLA)-matching algorithms is a prerequisite for the correct and efficient identification of optimal unrelated donors for patients requiring hematopoietic stem cell transplantation. The goal of this World Marrow Donor Association study was to validate established matching algorithms from different international donor registries by challenging them with simulated input data and subsequently comparing the output. This experiment addressed three specific aspects of HLA matching using different data sets for tasks of increasing complexity. The first two tasks targeted the traditional matching approach identifying discrepancies between patient and donor HLA genotypes by counting antigen and allele differences. Contemporary matching procedures predicting the probability for HLA identity using haplotype frequencies were addressed by the third task. In each task, the identified disparities between the results of the participating computer programs were analyzed, classified and quantified. This study led to a deep understanding of the algorithms participating and finally produced virtually identical results. The unresolved discrepancies total to less than 1%, 4% and 2% for the three tasks and are mostly because of individual decisions in the design of the programs. Based on these findings, reference results for the three input data sets were compiled that can be used to validate future matching algorithms and thus improve the quality of the global donor search process.
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Algoritmos , Alelos , Trasplante de Células Madre de Sangre del Cordón Umbilical , Antígenos HLA/genética , Trasplante de Células Madre Hematopoyéticas , Sistema de Registros , Conjuntos de Datos como Asunto , Frecuencia de los Genes , Antígenos HLA/clasificación , Antígenos HLA/inmunología , Haplotipos , Prueba de Histocompatibilidad , Humanos , Receptores de Trasplantes , Trasplante Homólogo , Donante no EmparentadoRESUMEN
We determined whether assessment of the immunogenicity of individual donor-recipient HLA mismatches based on differences in their amino-acid sequence and physiochemical properties predicts clinical outcome following haematopoietic SCT (HSCT). We examined patients transplanted with 9/10 single HLA class I-mismatched grafts (n=171) and 10/10 HLA-A-, -B-, -C-, -DRB1- and -DQB1-matched grafts (n=168). A computer algorithm was used to determine the physiochemical disparity (electrostatic mismatch score (EMS) and hydrophobic mismatch score (HMS)) of mismatched HLA class I specificities in the graft-versus-host direction. Patients transplanted with HLA-mismatched grafts with high EMS/HMS had increased incidence of ⩾grade II acute GVHD (aGVHD) compared with patients transplanted with low EMS/HMS grafts; patients transplanted with low and medium EMS/HMS grafts had similar incidence of aGVHD to patients transplanted with 10/10 HLA-matched grafts. Mortality was higher following single HLA-mismatched HSCT but was not correlated with HLA physiochemical disparity. Assessment of donor-recipient HLA incompatibility based on physiochemical HLA disparity may enable better selection of HLA-mismatched donors in HSCT.
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Bases de Datos Factuales , Enfermedad Injerto contra Huésped , Antígenos HLA , Trasplante de Células Madre Hematopoyéticas , Donante no Emparentado , Adolescente , Adulto , Algoritmos , Aloinjertos , Niño , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/mortalidad , Antígenos HLA/química , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Incidencia , Masculino , Países Bajos , Factores de RiesgoRESUMEN
HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor (UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06-1.53; P=0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37-0.80; P=0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.
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Epítopos de Linfocito T/inmunología , Cadenas alfa de HLA-DP/inmunología , Cadenas beta de HLA-DP/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Mapeo Epitopo , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Riesgo , Donante no Emparentado , Adulto JovenRESUMEN
INTRODUCTION: Previously we developed a weighted amino acid (AA) mismatch score predictive for cytotoxic T cell (CTL) alloreactivity (in vitro CTLp assay) based on the structure of the HLA class I molecule. The aim of this study is to confirm the clinical relevance of the CTLp assay and to validate the AA mismatch score as an alternative and easy to use tool to predict permissible mismatches in hematopoietic stem cell transplantation (HSCT). METHODS: We selected patients transplanted with a 9/10 single HLA class I mismatched graft (n=171) at three Dutch HSCT centers. A CTLp assay was performed in 73 donor-recipient pairs. As a control we selected 168 10/10 HLA matched pairs that were matched to the 9/10 single HLA class I mismatched pairs for HSCT year, donor type, patient age and diagnosis. RESULTS: We observed that pairs with negative a CTLp assay had statistically significant decreased incidence of mortality after HSCT comparable to that of 10/10 HLA matched pairs. However, the weighted AA mismatch score did not significantly predict any HSCT end point of interest. CONCLUSION: Further investigation is needed to unravel the mechanisms involved in causing the beneficial effect of a negative CTLp assay, before other alternative tools to predict HSCT outcome may be developed.
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Linfocitos T CD8-positivos/inmunología , Trasplante de Células Madre Hematopoyéticas , Antígenos de Histocompatibilidad Clase I/inmunología , Investigación Biomédica Traslacional , Donante no Emparentado , Adolescente , Adulto , Factores de Edad , Anciano , Aloinjertos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Países Bajos , Valor Predictivo de las PruebasRESUMEN
Estimation of human leukocyte antigen (HLA) haplotype frequencies from unrelated stem cell donor registries presents a challenge because of large sample sizes and heterogeneity of HLA typing data. For the 14th International HLA and Immunogenetics Workshop, five bioinformatics groups initiated the 'Registry Diversity Component' aiming to cross-validate and improve current haplotype estimation tools. Five datasets were derived from different donor registries and then used as input for five different computer programs for haplotype frequency estimation. Because of issues related to heterogeneity and complexity of HLA typing data identified in the initial phase, the same five implementations, and two new ones, were used on simulated datasets in a controlled experiment where the correct results were known a priori. These datasets contained various fractions of missing HLA-DR modeled after European haplotype frequencies. We measured the contribution of sampling fluctuation and estimation error to the deviation of the frequencies from their true values, finding equivalent contributions of each for the chosen samples. Because of patient-directed activities, selective prospective typing strategies and the variety and evolution of typing technology, some donors have more complete and better HLA data. In this setting, we show that restricting estimation to fully typed individuals introduces biases that could be overcome by including all donors in frequency estimation. Our study underlines the importance of critical review and validation of tools in registry-related activity and provides a sustainable framework for validating the computational tools used. Accurate frequencies are essential for match prediction to improve registry operations and to help more patients identify suitably matched donors.
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Antígenos HLA/inmunología , Haplotipos/inmunología , Prueba de Histocompatibilidad/normas , Modelos Estadísticos , Sistema de Registros , Programas Informáticos/normas , Trasplante de Células Madre , Frecuencia de los Genes , Antígenos HLA/genética , Prueba de Histocompatibilidad/métodos , Prueba de Histocompatibilidad/estadística & datos numéricos , Humanos , Donante no Emparentado/estadística & datos numéricosRESUMEN
For more than two decades, international cooperation and information technology have been playing key roles in the identification of suitable unrelated donors and cord blood units for hematopoietic SCT. To ensure consistent coding and interpretation of HLA data among the linked computer systems, the World Marrow Donor Association has standardized the extensions of the World Health Organization (WHO) Nomenclature for factors of the HLA system applied in practice. The first version of this report published in 2007 has become the reference for the technical validation of HLA information on donors and patients in the context of search and matching and is used by registries of volunteer unrelated hematopoietic stem cell donors and umbilical cord blood banks throughout the world. The present update became necessary after the major revision of the WHO HLA nomenclature in April 2010. It now covers issues arising when alleles are withdrawn or renamed because of the continuous updating of the WHO HLA nomenclature. In addition, formal validation and interpretation rules for the so-called 'multiple allele codes' have been added.
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Trasplante de Células Madre Hematopoyéticas/normas , Prueba de Histocompatibilidad/normas , Terminología como Asunto , Donantes de Tejidos , Guías como Asunto , Antígenos HLA/análisis , Antígenos HLA/inmunología , Humanos , Cooperación Internacional , Organización Mundial de la SaludRESUMEN
This project has the goal to validate bioinformatics methods and tools for HLA haplotype frequency analysis specifically addressing unique issues of haematopoietic stem cell registry data sets. In addition to generating new methods and tools for the analysis of registry data sets, the intent is to produce a comprehensive analysis of HLA data from 20 million donors from the Bone Marrow Donors Worldwide (BMDW) database. This report summarizes the activity on this project as of the 16IHIW meeting in Liverpool.
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Variación Genética , Antígenos HLA , Haplotipos , Biología Computacional , Frecuencia de los Genes , Antígenos HLA/genética , Antígenos HLA/inmunología , Haplotipos/genética , Haplotipos/inmunología , Humanos , Sistema de Registros , Donantes de TejidosRESUMEN
The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients' haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing ≥ grade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31-0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or -B, and HLA-C or -B and -DRB1 (HR (95% CI): 0.49 (0.26-0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of ≥ grade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes.
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Selección de Donante/métodos , Enfermedad Injerto contra Huésped/mortalidad , Antígenos HLA , Haplotipos , Trasplante de Células Madre Hematopoyéticas , Desequilibrio de Ligamiento , Donante no Emparentado , Enfermedad Aguda , Adolescente , Adulto , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/prevención & control , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
To investigate whether all patients in need of an allogeneic hematopoietic SCT (HSCT) are offered one, we retrospectively investigated the policy for all children diagnosed with myelodysplastic syndrome (n=90) or relapsed AML (n=75) between 1998 and 2008. These children are registered at diagnosis and treated according to protocols of the Dutch Childhood Oncology Group, which provides accurate disease incidence data and protocol-indicated appropriateness for HSCT. For 48 (30%) patients, a family donor was identified; for 90 (57%) patients, an unrelated donor (UD) search was performed; and for 21 (13%) patients, no UD search was initiated. Reasons for not initiating an UD search include: progressive disease (n=10), conserve quality of life (n=1), stable disease (n=3), immunosuppressive therapy (n=2), patient death (n=3), patient lives abroad (n=1) and second relapse (n=1). On the basis of the time interval between date of diagnosis and date of death/last follow-up, for eight (5%) patients, it may be questioned why an UD search was not performed. The fact that 95% of all children are given the option of an allogeneic HSCT is encouraging and reasons not to transplant seem fair in most cases.
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Accesibilidad a los Servicios de Salud , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/terapia , Adolescente , Niño , Preescolar , Femenino , Humanos , Países Bajos , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo , Donante no EmparentadoRESUMEN
Many parameters predict for outcome after unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (alloSCT). High-resolution HLA-matching significantly impacts outcome and also the European Group of Blood and Marrow Transplantation (EBMT) risk score, based on patient age, disease stage, donor type, time from diagnosis to SCT and gender combination, may predict for non-relapse mortality and overall survival (OS). We evaluated the individual and combined effects of allele-matching and the EBMT risk score in 327 patients with poor-risk acute leukemia or myelodysplasia, who received a T-cell depleted URD alloSCT. Matching for HLA-A, -B, -C and -DRB1 alleles (8/8 match) was associated with a 5-year OS of 40% compared with 30% for mismatched (≤7/8) pairs (P=0.02). Patients with EBMT risk scores of 1-2, 3, 4 and 5-7 had 5-year OS estimates of 53, 43, 30 and 20%, respectively (P<0.001). The favorable prognostic impact of an 8/8 donor was most pronounced if the EBMT risk score was low (1-2). Five-year OS was 74±8% vs 39±11% for fully matched patients with a low-risk EBMT score as compared with EBMT low-risk patients with ≤7/8 donors. These data underscore the importance of incorporating both the EBMT risk score and the degree of high-resolution HLA-matching in the risk assessment prior to URD alloSCT.
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Alelos , Trasplante de Médula Ósea , Leucemia/cirugía , Síndromes Mielodisplásicos/cirugía , Linfocitos T/citología , Enfermedad Aguda , Adulto , Femenino , Prueba de Histocompatibilidad , Humanos , Leucemia/genética , Masculino , Síndromes Mielodisplásicos/genética , Recurrencia , RiesgoRESUMEN
A major goal of the World Marrow Donor Association (WMDA) is to foster international transplants of hematopoietic stem cells through the establishment of guidelines and recommendations in this field. In this tradition, this study defines a comprehensive framework for HLA matching programs, which use intricate algorithms to rapidly select potential donors for a patient from a database and to present these donors in a prioritized list. Starting with the comparison of single HLA markers of the donor and the patient possibly obtained using different testing methodologies at different resolutions, the more complex matching of loci and phenotypes is inductively built up. The consensus of this international collaborative group describes the state of the art in the field and points out many important design options compatible with the best practice. This should help existing registries to review and validate the most critical part of their IT systems and newly created donor registries around the world to tackle one of their real challenges.
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Bancos de Sangre/normas , Sangre Fetal/inmunología , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/inmunología , Prueba de Histocompatibilidad/normas , Sistema de Registros/normas , Trasplante de Médula Ósea/métodos , Prueba de Histocompatibilidad/métodos , Humanos , Donantes de Tejidos , Organización Mundial de la SaludRESUMEN
The World Marrow Donor Association Annual Reports describe the current status of the use of unrelated hematopoietic cell products worldwide. In 2008, almost 1.7 million individuals were recruited into unrelated stem cell donor registries and almost 78 000 cord blood units were added to the inventory increasing the total number of available stem cell donors worldwide to over 14 million. In 2008, there were 10 481 adult stem cell donations (3221 BM and 7260 PBSC donations) provided from stem cell donor registries in 38 countries. In 2008, 3529 cord blood products were provided from 21 countries. Although the number of BM donations has been stable over the past 10 years, donations of PBSCs and umbilical cord blood are increasing.
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Informes Anuales como Asunto , Trasplante de Células Madre Hematopoyéticas/normas , Internacionalidad , Donantes de Tejidos , Obtención de Tejidos y Órganos/normas , Humanos , Sistema de Registros/normas , Donantes de Tejidos/provisión & distribución , Trasplante HomólogoRESUMEN
The transplant policy for unrelated donor (UD) BMT at Leiden Paediatrics' SCT-Centre consisted of the use of (1) fully HLA-matched donors or, if not available, HLA-class I matched and/or cytotoxic T-lymphocyte precursor (CTLp)-negative donors and (2) protective isolation of the recipient and antimicrobial suppression of his/her gut microflora to prevent infections and acute GVHD. Engraftment, GVHD, relapse in the case of malignancy and survival were studied retrospectively in 126 evaluable children, transplanted between 1988 and 2005. In addition to the effect of HLA-matching, that of other transplant-relevant variables on the outcome was also studied. Actuarial OS was 65% and the EFS was 59%, 13% graft failures occurred and 7.5% > or =grade II acute GVHD. HLA-class II mismatches combined with HLA-class I matches resulted in a superior OS of 92%, as did a negative vs positive CTLp test, that is, 65 vs 33%. Analysis of other variables showed a poorer OS in patients > or =10 yrs vs <10 yrs, that is, 54 vs 73%, and in male recipients of a female donor graft, that is, 53 vs 69% for other combinations. UD-BMT can be optimized by permitting HLA-class I-matched and/or CTLp-negative donors, and probably by choosing male donors for male recipients.
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Trasplante de Médula Ósea/métodos , Política de Salud , Adolescente , Trasplante de Médula Ósea/inmunología , Trasplante de Médula Ósea/mortalidad , Niño , Preescolar , Femenino , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Enfermedad Injerto contra Huésped/inmunología , Antígenos HLA/inmunología , Prueba de Histocompatibilidad , Humanos , Lactante , Masculino , Recurrencia Local de Neoplasia/inmunología , Países Bajos/epidemiología , Aislamiento de Pacientes , Estudios Retrospectivos , Donantes de Tejidos , Resultado del TratamientoRESUMEN
Thirty-six novel human leukocyte antigen (HLA) alleles are described in this article: A*9225N, A*9234, A*030106, A*0337, A*2317, A*2480, A*3023; B*070206, B*0759, B*0761, B*0765, B*150106, B*1827, B*352002, B*3585, B*3943, B*4082, B*5151; Cw*0342, Cw*0343, Cw*0344, Cw*0428, Cw*0430, Cw*0433, Cw*050104, Cw*0519, Cw*060203, Cw*070109, Cw*070202, Cw*0750, Cw*0815, Cw*120306, Cw*1409; DRB1*0336, DRB1*0473 and DRB1*1382.
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Alelos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DR/genética , Análisis Mutacional de ADN , Cadenas HLA-DRB1 , Prueba de Histocompatibilidad/métodos , Humanos , Datos de Secuencia Molecular , Polimorfismo de Nucleótido SimpleRESUMEN
On 16 November 2005, we celebrated the milestone when 10 million donors had been registered in Bone Marrow Donors Worldwide (BMDW). Since then another million donors have been added in little more than a year. It seems an appropriate time for reassessment and to ask whether we are on the right track or not. We will do so by discussing the strength, weaknesses, opportunities and threats of the unrelated stem cell donor operation.
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Trasplante de Médula Ósea , Donantes de Tejidos , Trasplante de Médula Ósea/mortalidad , Enfermedad Injerto contra Huésped/etiología , Prueba de Histocompatibilidad , Humanos , Sistema de Registros , Factores de Tiempo , Obtención de Tejidos y ÓrganosRESUMEN
A fully major histocompatilbility complex (MHC) matched donor is not available for the majority of patients in need of a haematopoietic stem cell transplantation (SCT), which illustrates the need for a tool to define acceptable MHC disparities. Previously, we noticed that a variety of single MHC class I mismatched allogeneic donor-recipient pairs did not elicit an allogeneic cytotoxic-lymphocyte (CTL) response in vitro if the MHC amino-acid sequences had five or more differences in the alpha-helices plus five or more differences in the beta-sheet (> or =5alpha5beta) (7). To address the clinical relevance of this observation, we analysed CTL precursor (CTLp) assay outcome and SCT outcome in 53 Dutch recipients of a single MHC class I mismatched graft from an unrelated donor. Overall patient survival was 44% after 4 years. In multivariate analysis, recipients of a > or =5alpha5beta mismatched graft with negative CTLp frequencies in vitro before transplantation demonstrated superior survival: survival at 4 years was 80% as compared to 47% in recipients of other mismatched grafts with negative CTLp frequencies (hazard ratio=0.131; 95% CI=(0.03-0.61); P=0.009). This option of acceptable mismatches may enlarge the pool of potentially acceptable stem cell donors.
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Trasplante de Células Madre Hematopoyéticas , Antígenos de Histocompatibilidad Clase I , Histocompatibilidad , Donadores Vivos , Adolescente , Adulto , Anciano , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/mortalidad , Enfermedades Autoinmunes/terapia , Linfocitos T CD8-positivos/inmunología , Niño , Preescolar , Selección de Donante , Femenino , Estudios de Seguimiento , Enfermedades Genéticas Congénitas/mortalidad , Enfermedades Genéticas Congénitas/terapia , Enfermedades Hematológicas/inmunología , Enfermedades Hematológicas/mortalidad , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/mortalidad , Histocompatibilidad/genética , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Lactante , Masculino , Persona de Mediana Edad , Países Bajos , Estructura Secundaria de Proteína , Tasa de Supervivencia , Trasplante HomólogoRESUMEN
Over 10 million volunteer donors and cord blood units are typed for human leukocyte antigen (HLA) within hematopoietic stem cell registries and cord blood banks. Identification of matched donors in countries different from that of the searching patient is facilitated by Bone Marrow Donors Worldwide and the World Marrow Donor Association (WMDA). A survey of new volunteer donor typing among WMDA member registries has identified the methods and resolution of HLA testing and the level of quality control used to evaluate the accuracy of typing results. The diversity of HLA assignments within registries has generated a number of informatics challenges. Registries are using population genetics to enhance registry diversity and to facilitate the identification of matched donors.
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Algoritmos , Variación Genética , Antígenos HLA/genética , Prueba de Histocompatibilidad/métodos , Sistema de Registros , Donantes de Tejidos/provisión & distribución , Antígenos HLA/clasificación , HumanosRESUMEN
The goal was to establish the best typing techniques and strategies for donors selected as potential donors for a specific patient. Complete sequence of exons 2 and 3 for class I and exon 2 for class II molecules by sequencing-based typing was deemed the best technique in reducing problems with ambiguities and null alleles as well as the possibility to establish a completely automated system. Focusing on multiple approaches for typing was regarded as a better strategy than continued usage of serological methods although the latter technique was still considered to be useful by some for detection of null alleles. The patient and finally the selected donor, including the back-up donor, should be typed for at the highest level and typing ambiguities should be resolved. In very difficult cases, race, haplotype information and allele frequency in the population should help to decide whether or not to resolve the ambiguity. Cellular techniques such as the cytotoxic T lymphocyte precursor test may help to choose between single class I mismatched donors in experienced laboratories only.