Dataset Information

Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

ABSTRACT: Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates. This DNA-based test is capable of simultaneously typing most clinically relevant red blood cell (RBC), human platelet (HPA), and human leukocyte (HLA) antigens. Validation was performed, using samples from 7927 European, 27 South Asian, 21 East Asian, and 9 African blood donors enrolled in 2 national biobanks. We illustrated the usefulness of the platform by analyzing antibody data from patients sensitized with multiple RBC alloantibodies. Genotyping results demonstrated concordance of 99.91%, 99.97%, and 99.03% with RBC, HPA, and HLA clinically validated typing results in 89 371, 3016, and 9289 comparisons, respectively. Genotyping increased the total number of antigen typing results available from 110 980 to >1 200 000. Dense donor typing allowed identification of 2 to 6 times more compatible donors to serve 3146 patients with multiple RBC alloantibodies, providing at least 1 match for 176 individuals for whom previously no blood could be found among the same donors. This genotyping technology is already being used to type thousands of donors taking part in national genotyping studies. Extraction of dense antigen-typing data from these cohorts provides blood supply organizations with the opportunity to implement a policy of genomics-based precision matching of blood.

SUBMITTER: Gleadall NS

PROVIDER: S-EPMC7422129 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

Gleadall Nicholas S NS Veldhuisen Barbera B Gollub Jeremy J Butterworth Adam S AS Ord John J Penkett Christopher J CJ Timmer Tiffany C TC Sauer Carolin M CM van der Bolt Nieke N Brown Colin C Brugger Kim K Dilthey Alexander T AT Duarte Daniel D Grimsley Shane S van den Hurk Katja K Jongerius John M JM Luken Jessie J Megy Karyn K Miflin Gail G Nelson Christopher S CS Prinsze Femmeke J FJ Sambrook Jennifer J Simeoni Ilenia I Sweeting Michael M Thornton Nicole N Trompeter Sara S Tuna Salih S Varma Ram R Walker Matthew R MR Danesh John J Roberts David J DJ Ouwehand Willem H WH Stirrups Kathleen E KE Rendon Augusto A Westhoff Connie M CM Di Angelantonio Emanuele E van der Schoot C Ellen CE Astle William J WJ Watkins Nicholas A NA Lane William J WJ

Blood advances 20200801 15

Each year, blood transfusions save millions of lives. However, under current blood-matching practices, sensitization to non-self-antigens is an unavoidable adverse side effect of transfusion. We describe a universal donor typing platform that could be adopted by blood services worldwide to facilitate a universal extended blood-matching policy and reduce sensitization rates. This DNA-based test is capable of simultaneously typing most clinically relevant red blood cell (RBC), human platelet (HPA) ...[more]

PMID: 32750130

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Project description:Purpose Coa and Cob antigens of the Colton (CO) blood group system are implicated in acute and delayed hemolytic transfusion reactions (HTRs). Owing to the inadequate supply of specific antiserum, data on CO phenotypes remain limited. This study aimed to develop genotyping methods to predict Coa and Cob antigens and to estimate transfusion-induced alloimmunization risks in three Thai blood donor populations. Materials and Methods The study included 2451 blood samples from unrelated healthy Thai blood donors obtained from central, northern, and southern Thailand. DNA sequencing was used to determine the CO*A and CO*B alleles. In-house PCR with sequence-specific primers (PCR-SSP) and high-resolution melting curve (HRM) assays were performed and genotyping results were compared using DNA sequencing. CO*A and CO*B allele frequencies among Thais were determined using PCR-SSP and their frequencies were compared with other populations. The risks of Coa and Cob transfusion-induced alloimmunization among Thai donor populations were calculated. Results The validated genotyping results by PCR-SSP and HRM assays agreed with DNA sequencing. The CO*A/CO*A was the most common (100.0, 100.0, and 99.3%), followed by CO*A/CO*B (0.0, 0.0, and 0.7%) among central, northern and southern Thais. Homozygous CO*B/CO*B was not found. The CO*A and CO*B allele frequencies among central Thais significantly differed compared among southern Thais (p < 0.01) but not among northern Thais. Those allele frequencies among Thais were similar to those of Taiwanese, Chinese and Malay-Malaysian populations but not to South Asian, Southeast Asian, Korean, Japanese, Filipino, French Basque, and Maltese populations (p < 0.01). A higher risk of anti-Cob production rather than anti-Coa production was particularly noted in the southern Thai population. Conclusion This study constitutes the first to determine CO*A and CO*B genotypes using PCR-SSP and HRM assays among Thais and this finding would be beneficial in predicting alloimmunization risk and providing safe transfusions among Thais.

Project description:BackgroundEpilepsy, multiple sclerosis (MS), and depression are chronic conditions where technology holds potential in clinical monitoring and self-management. Over 5 years, the Remote Assessment of Disease and Relapse - Central Nervous System (RADAR-CNS) consortium has explored the application of remote measurement technology (RMT) to the management and self-management of patients in these clinical areas. The consortium is large and includes clinical and nonclinical researchers as well as a patient advisory board.ObjectiveThis formative development study aimed to understand how consortium members viewed the potential of RMT in epilepsy, MS, and depression.MethodsIn this qualitative survey study, we developed a methodological tool, universal points of care (UPOC), to gather views on the potential use, acceptance, and value of a novel RMT platform across 3 chronic conditions (MS, epilepsy, and depression). UPOC builds upon use case scenario methodology, using expert elicitation and analysis of care pathways to develop scenarios applicable across multiple conditions. After developing scenarios, we elicited views on the potential of RMT in these different scenarios through a survey administered to 28 subject matter experts, consisting of 16 health care practitioners; 5 health care services researchers; and 7 people with lived experience of MS, epilepsy, or depression. Survey results were analyzed thematically and using an existing framework of factors describing links between design and context.ResultsThe survey elicited potential beneficial applications of the RADAR-CNS RMT system as well as patient, clinical, and nonclinical requirements of RMT across the 3 conditions of interest. Potential applications included recognition of early warning signs of relapse from subclinical signals for MS, seizure precipitant signals for epilepsy, and behavior change in depression. RMT was also thought to have the potential to overcome the problem of underreporting, which is especially problematic in epilepsy, and to allow the capture of secondary symptoms that are not generally collected in MS, such as mood.ConclusionsRespondents suggested novel and unanticipated uses of RMT, including the use of RMT to detect emerging side effects of treatment, enable behavior change for sleep regulation and activity, and offer a way to include family and other carers in a care network, which could assist with goal setting. These suggestions, together with others from this and related work, will inform the development of the system for its eventual application in research and clinical practice. The UPOC methodology was effective in directing respondents to consider the value of health care technologies in condition-specific experiences of everyday life and working practice.

Dataset Information

Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

Publications

Development and validation of a universal blood donor genotyping platform: a multinational prospective study.

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