External proficiency testing for histocompatibility and immunogenetics in today and future.

The Histocompatibility and Immunogenetics laboratories provide disease association and pharmacogenetic analyses as well as the tests required for transplantation immunology and transfusion medicine. They perform Human Leukocyte Antigen (HLA) genotyping in patients/recipients and potential donor candidates for solid organ and stem cell transplants using various molecular methods, and determine mismatches. In addition, they also perform HLA antibody tests to detect anti-HLA antibodies in patients and flow cross-matches to evaluate donor-recipient compatibility. Evidence-based clinical guidelines have emphasized the importance of laboratory tests in clinical practices for a long time. Understanding the principles of Quality Control and External Quality Assurance is a fundamental requirement for the effective management of Tissue Typing laboratories. When these processes are effectively implemented, errors in routine assays for transplantation are reduced and quality is improved. In this review, the importance of Quality Assurance, Quality control and proficiency testing in Histocompatibility and Immunogenetic testing, the necessity of external proficiency testing (EPT) for accreditation, and existing and potential EPT programmes will be reviewed and evaluated in the light of the literature.

Population genetics and external proficiency testing for HLA disease associations.

Numerous associations of HLA variants with susceptibility to diseases, namely, those with an immunopathological component, have been described to date. The strongest HLA associations were incorporated into the standard algorithms for the diagnostics. Disease-associated HLA variants are routinely detected by various techniques including DNA-based assays. For the identification of HLA markers or their combinations with the highest diagnostic value and those with frequent clinical indications (e.g., HLA-B*27, -B*57:01, -DQ2/-DQ8, -DQB1*06:02), diagnostic tests that focus on a single or limited number of specific HLA antigens/alleles, have already been developed; the use of complete typing for particular HLA loci is a relevant alternative. Importantly, external proficiency testing (EPT) became an integral part of good laboratory practice for HLA disease associations in accredited laboratories and not only supports correct "technical" identification of the associated HLA variants, but also adequate interpretation of the results to the clinicians. In the present article selected aspects of EPT for HLA disease associations related to population genetics are reviewed and discussed with the emphasis on the optimal level of HLA typing resolution, population-based differences in disease associated HLA alleles within the allelic group, distribution and linkage disequilibrium of HLA alleles in particular populations and interpretation of the presence of less common HLA variants/haplotypes. In conclusion, the laboratories that perform and interpret the tests to the clinicians, producers of the certified diagnostics and EPT providers should consider, among others, the genetic characteristics of the populations in order to optimise the diagnostic value of the tests for disease-associated HLA variants.

The history and evolution of HLA typing external proficiency testing schemes in UK NEQAS for H&I.

The UK National External Quality Assessment Service (NEQAS) provide an external proficiency testing (EPT) service for clinical laboratories. UK NEQAS for Histocompatibility and Immunogenetics (H&I) has been providing EPT schemes for over 45 years and has grown during this time to provide 19 EPT schemes. Accurate human leucocyte antigen (HLA) typing is critical to support safe clinical services, including transplantation, therefore high quality, relevant EPT schemes are required as part of a laboratory's quality assurance. This article reviews the development of the HLA typing EPT schemes, from the first HLA phenotyping scheme in 1975, via the first HLA genotyping scheme in 1992, through to the introduction in 2017 of HLA third field assessment results from next-generation sequencing technology. In addition, the introduction of EPT schemes to cover HLA associated diseases and pharmacogenetic reactions, including HLA-B27, HLA*B*57:01 and HLA-DQ for coeliac disease are discussed. The accuracy of laboratory EPT results for HLA phenotyping are >96% (2018-2022), HLA genotyping >99% (2020-2022), HLA-B27 testing >99% (2018-2022) and B*57:01 testing >99% (2017-2022). However, for HLA genotyping for coeliac disease 22%-46% of laboratories made errors in 2020-2022. On investigation, the high rate of unsatisfactory performance was attributed to laboratories lacking specific knowledge to interpret HLA genotyping results and accurately report HLA types for coeliac disease. A misleading commercial kit insert was also identified. The assessment of scheme results has uncovered several issues which have been addressed with the intention of educating participants and improving clinical services. The UK NEQAS for H&I EPT schemes have evolved over the past four decades to reflect changes in HLA typing technology, laboratory clinical practice and to cover post-analytical interpretative elements of HLA typing.

Accreditation of histocompatibility and immunogenetics laboratories: Achievements and future prospects from the European Federation for Immunogenetics Accreditation Programme.

The importance of demonstrating adherence to good practice in the provision of clinical services is well recognised, and there are many legislative and regulatory requirements that aim to ensure that services are appropriately reviewed and certified. Therefore, for regulatory purposes, laboratories must provide assurance of the quality of the services they provide. Additionally in the field of transplantation, where donor organs and stem cells are exchanged across national boundaries, adoption of a common set of standards by laboratories across many different countries is an important factor. The European Federation for Immunogenetics (EFI) Accreditation Programme was established to provide assurance that Histocompatibility & Immunogenetics laboratories providing services for transplantation, transfusion, and disease association testing meet the requirements of the specialty specific EFI standards. The first H&I laboratories achieved EFI accreditation in 1995, and currently there are over 260 EFI accredited laboratories in 36 countries. The programme depends on the voluntary participation of the inspectors, who are all experts in the field of H&I, and who, over the last 22 years, have performed over 1400 onsite inspections of laboratories. Inspection findings show the areas that are most frequently found to be deficient in meeting the requirements of the standards, and this can be used to inform educational and other activities with the aim of improving laboratory compliance with the standards. The EFI standards have been regularly updated to reflect the changes in the field with 19 versions over the last 22 years, and the data from the accreditation programme show how laboratories have changed their practices to incorporate new techniques that support patient care.

Report on External Proficiency Testing for the ABO and D Blood Group Typing Tests in Blood Centers (2014) / 대한수혈학회지

BACKGROUND: Korean Blood Safety Commission has implemented external proficiency testing (PT) for blood grouping test (BGT) to help improve the quality of blood centers since 2011. We analyzed the results of 2014 PT for BGT to help in planning the future PT for BGT and to improve the quality of blood centers. METHODS: Whole blood survey samples including three panels for ABO grouping and three panels for D typing were sent to 69 institutes. Evaluation criteria for BGT were as follows: 'Good' for answers matched with intended results, 'Acceptable' for correct answers other than that of 'Good', 'Unacceptable' for answers other than those of 'Good+acceptable' as correct answers; and 'Not graded' for answers in case of different answers in the two standard laboratories. RESULTS: All of the answer rates of 'Good' for D typing were 100%. However, the answer rates of 'Good' for cell typing, serum typing and interpretation for 14-ABO-2 samples with discrepant result between cell typing and serum typing were 39.1%, 29%, and 47.8%, respectively. Those of 'Unacceptable' for cell typing and interpretation for 14-ABO-2 samples were 2.8% and 1.4%. CONCLUSION: Because the answer rates of ABO grouping for samples with discrepant result between cell typing and serum typing were not high, education for this case is needed. Diversity of materials for PT would be necessary for more accurate evaluation of the performance of BGT in blood centers.

Report on External Proficiency Testing for the ABO and D Blood Typing in Blood Centers in 2012 and 2013 / 대한수혈학회지

BACKGROUND: It was reported that a continuous education program and external proficiency testing (PT) for blood grouping test (BGT) might be necessary because some blood centers of medical institutions could not correctly examine ABO subtype and D variant, according to the results of the first year project in 2011. Therefore, the results of PT for BGT in blood centers in 2012 and 2013 were compared to those in 2011 in order to assess the impact of projects during a period of three years and to help in planning the future PT for BGT. METHODS: Whole blood survey samples composed of three panels for ABO grouping and three panels for D typing were sent to 74 and 71 institutes in 2012 and 2013, respectively. Evaluation criteria for BGT were as follows: 'Good' for the answers matched with intended results, 'Acceptable' for the correct answers other than that of 'Good', and 'Unacceptable' for the answers other than those of 'Good+acceptable' as correct answers. RESULTS: The answer rates of 'Unacceptable' for ABO subtype were 1.4% in 2012 and 4.2% in 2013. However, the answer rate of 'Good' increased from 44.6% in 2012 to 83.1% in 2013. The answer rate of 'Unacceptable' for D variants showed a marked decrease, from 16.2% in 2012 to 1.4% in 2013. CONCLUSION: Projects for PT for BGT during a period of three years have improved laboratory quality in blood centers. However, the acquisition and change of the materials for PT would be necessary in order to continuously and practically provide help to blood centers.

Report on External Proficiency Testing for Blood Grouping Tests in Blood Centers (2011) / 대한수혈학회지

BACKGROUND: To ensure safety of blood transfusion, accuracy in performance of blood grouping tests (BGT) is essential. External proficiency testing (PT) for BGT has not been conducted in Korea. The first PT for BGT in domestic blood centers was conducted in order to evaluate the domestic status of accuracy of BGT in blood centers and to aid in improving the quality of blood centers. METHODS: Whole blood survey specimens consisting of three panels for ABO grouping and two panels for Rh typing were sent to 81 blood centers. Evaluation criteria for BGT were as follows: 'Good' for answers with 100% referee consensus, 'Acceptable' for correct answers other than those of the referee, and 'Unacceptable' for answers other than those of 'Good+acceptable' as correct answers. RESULTS: Rates of correct answers on three panels for ABO grouping were all 100%; however, that of cell typing for the panel with BW was 61.7%, and 31 blood centers incorrectly reported normal 'B' type as an answer. The rate of correct answers for the Rh negative panel was 100%; however, that for the weak D panel was 84%, and 13 blood centers incorrectly reported Rh negative type as an answer. CONCLUSION: Findings from this study demonstrated that some hospital blood centers were not able to correctly detect blood groups with weak antigens. Therefore, to improve the quality of blood centers, intensive education for blood center staff and continued PT for BGT should be required.

External Quality Assurance Survey for the Blood Donor Screening Tests Performed in 2010 / 대한수혈학회지

BACKGROUND: To prevent blood-borne infections and guarantee safe transfusion, we proposed a quality assurance program for donor screening tests, such as hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibody (anti-HCV), by introducing external proficiency testing for the laboratories that perform donor screening tests. METHODS: The materials for external proficiency testing (PT) were prepared from the HBsAg Standard Panels and anti-HCV Reference Panels provided by the Korea Food and Drug Administration (KFDA), and the normal Human Serum was provided by the Serum Bank of the Korea National Research Resource Center. The external PT materials were sent to 83 laboratories that performed donor screening tests after evaluating their quality. RESULTS: The results of evaluating the quality of the PT materials were acceptable. All the laboratories receiving the materials answered with a 100% response rate. All the laboratories answered that they obtained positive results for the HBsAg Standard Panel E, H, I and J; however, one laboratory answered in the gray-zone and that lab had negative results for HBsAg Standard Panel C and G. Seventy laboratories (84%) and 42 laboratories (51%) among the total 83 laboratories answered they had positive results for HBsAg Standard Panel B and D, suggesting that many laboratories could not detect a low level of HBsAg. All 83 laboratories answered that they had concordant results for the external PT for anti-HCV. CONCLUSION: Donor screening laboratories can detect low levels of HBsAg and anti-HCV without any errors and the performance of the laboratories that could not detect low levels of HBsAg remains to be improved. Quality assurance program using external PT with materials that contain various genotypes and mutants should be conducted to maintain the quality of donor screening tests.