Clinical Pharmacogenetic Testing and Application: 2024 Updated Guidelines by the Korean Society of Laboratory Medicine.

In the era of precision medicine, pharmacogenetics has substantial potential for addressing inter-individual variability in drug responses. Although pharmacogenetics has been a research focus for many years, resulting in the establishment of several formal guidelines, its clinical implementation remains limited to several gene-drug combinations in most countries, including Korea. The main causes of delayed implementation are technical challenges in genotyping and knowledge gaps among healthcare providers; therefore, clinical laboratories play a critical role in the timely implementation of pharmacogenetics.

Effects of Various Concentrations of Pronase on Flow Cytometric Crossmatching Patients Treated With Rituximab and Donor HLA-Specific Antibodies.

Background: Pronase pretreatment can reduce rituximab (RTX) interference by degrading CD20 in B-cell flow cytometry crossmatch (FCXM) testing. However, it may also reduce the assay sensitivity by degrading HLA molecules. We investigated the effects of various pronase concentrations on RTX interference and the analytical sensitivity of B-cell FCXM testing.

The time-dependent changes in serum immunoglobulin after kidney transplantation and its association with infection.

Introduction: Kidney transplant recipients often experience significant alterations in their immune system, which can lead to increased susceptibility to infections. This study aimed to analyze time-dependent changes in serum immunoglobulin and complement levels and determine the risk factors associated with infection.

Methods: A retrospective analysis of serum samples from 192 kidney transplant recipients who received transplantations between August 2016 and December 2019 was conducted.

Clinical Practice Guideline for Blood-based Circulating Tumor DNA Assays.

Circulating tumor DNA (ctDNA) has emerged as a promising tool for various clinical applications, including early diagnosis, therapeutic target identification, treatment response monitoring, prognosis evaluation, and minimal residual disease detection. Consequently, ctDNA assays have been incorporated into clinical practice. In this review, we offer an in-depth exploration of the clinical implementation of ctDNA assays.

Characterization of novel HLA-A*24:608N allele discovered in Koreans.

A novel null HLA-A*24 allele, HLA-A*24:608N, was identified in five Korean subjects including three from a family and two separate individuals. This study was performed to discern its immunological function in transplantation settings. Because this null variant had deletions of approximately 12 k base pairs from intron 3 to 3' end of the HLA-A gene, low resolution HLA typing and amplicon-based next generation sequencing (NGS) typing methods had failed to assign it.

Association Between Low Anti-spike Antibody Levels After the Third Dose of SARS-CoV-2 Vaccination and Hospitalization due to Symptomatic Breakthrough Infection in Kidney Transplant Recipients.

Background: Whether anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels post-third coronavirus disease (COVID-19) vaccination correlate with worse outcomes due to breakthrough infection is unclear. We evaluated the association between anti-SARS-CoV-2 antibody levels and symptomatic breakthrough infection or hospitalization during the Omicron surge in kidney transplant recipients.

Methods: In total, 287 kidney transplant recipients expected to receive a third vaccination were enrolled between November 2021 and February 2022.

A voluntary transfusion recipient registry in Korea as a database for blood group antibodies.

Background: Several types of transfusion-related registries have been developed to improve patient outcomes and blood banks. In Korea, a transfusion program functioning as a blood group antibody database and a reference laboratory has been in operation since July 2013. This study was conducted to determine the current status of blood group antigens and antibodies in Korea and propose a model for registries in the field of transfusion medicine.

Comparison of Four T-cell Assays and Two Binding Antibody Assays in SARS-CoV-2 Vaccinees With or Without Omicron Breakthrough Infection.

Background: Several T-cell response assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are available; however, their comparability and correlations with antibody responses remain unclear. We compared four SARS-CoV-2 T-cell response assays and two anti-SARS-CoV-2 spike antibody assays.

Methods: We enrolled 89 participants who had received a booster dose of the BNT162b2 vaccine after two doses of the ChAdOx1 or BNT162b2 vaccine.

Allele and haplotype frequencies of 11 HLA loci in Koreans by next-generation sequencing.

Data on HLA genotype distribution, including DQA1 and DPA1, in the Korean population are limited. We aimed to investigate the allele and haplotype frequencies of 11 HLA loci in 339 Korean subjects using next-generation sequencing (NGS)-based HLA typing. A total of 339 samples from unrelated healthy subjects were genotyped for HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1, -DQA1, -DPB1, and -DPA1 using two different NGS-based HLA typing kits (166 tested using the NGSgo-MX11-3 kit [GenDx, Netherlands] and 173 by the AllType NGS 11 Loci Amplification kit [One Lambda, USA]).

Clinical Significances of Anti-Collagen Type I and Type III Antibodies in Antibody-Mediated Rejection.

It is important to determine the clinical significance of non-human leukocyte antigen (HLA) antibodies and their association with antibody-mediated rejection (ABMR) of kidney allografts. We collected post-transplant sera from 68 ABMR patients, 67 T-cell mediated rejection (TCMR) patients, and 83 control subjects without rejection, and determined the titers of 39 non-HLA antibodies including antibodies for angiotensin II receptor type I and MICA. We compared all these non-HLA antibody titers among the study groups.

Differences in the diagnosis and treatment of hematologic malignancies attributable to health insurance coverage.

Medical care should be equally provided to the public regardless of their financial capability. In the real world, expenditures directly out from the patient sector decide the medical journey, even in a country with national health insurance. The aim of this study was to investigate whether there are differences in the diagnostic and treatment processes in hematologic malignancies based on patient characteristics, such as health insurance status.

Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored human leukocyte antigen genotypes.

Background: Several type B adverse drug reactions (ADRs), especially severe cutaneous adverse reactions (SCARs), are associated with particular human leukocyte antigen (HLA) genotypes. However, pre-stored HLA information obtained from other clinical workups has not been used to prevent ADRs. We aimed to simulate the preemptive use of pre-stored HLA information in electronic medical records to evaluate whether this information can prevent ADRs.

SARS-CoV-2 Omicron Mutation Is Faster than the Chase: Multiple Mutations on Spike/ACE2 Interaction Residues.

Recently, a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (B.1.1.

Association of HLA-DRB1 and -DQB1 Alleles with Susceptibility to IgA Nephropathy in Korean Patients.

Background: Associations between IgA nephropathy (IgAN) and HLA-DRB1 and -DQB1 alleles have been reported in several ethnic groups. We investigated the association of HLA-DRB1 and -DQB1 alleles with the predisposition for IgAN and disease progression to end-stage kidney disease (ESKD) in Korean patients.

Methods: We analyzed HLA-DRB1 and -DQB1 genotypes in 399 IgAN patients between January 2000 and January 2019 using a LIFECODES sequence-specific oligonucleotide (SSO) typing kit (Immucor, Stamford, CT, USA) or a LABType SSO Typing Test (One Lambda, Canoga Park, CA, USA).

Performance evaluation of three automated quantitative immunoassays and their correlation with a surrogate virus neutralization test in coronavirus disease 19 patients and pre-pandemic controls.

Background: SARS-CoV-2 pandemic is currently ongoing, meanwhile vaccinations are rapidly underway in some countries. The quantitative immunoassays detecting antibodies against spike antigen of SARS-CoV-2 have been developed based on the findings that they have a better correlation with the neutralizing antibody.

Methods: The performances of the Abbott Architect SARS-CoV-2 IgG II Quant, DiaSorin LIAISON SARS-CoV-2 TrimericS IgG, and Roche Elecsys anti-SARS-CoV-2 S were evaluated on 173 sera from 126 SARS-CoV-2 patients and 151 pre-pandemic sera.

Role of the IL-33/ST2 pathway in renal allograft rejection.

The interleukin-33 (IL-33)/suppression of tumorigenicity 2 (ST2) pathway modulates immune response and inflammation, associated with allograft dysfunction and rejection. We hypothesized that IL-33/ST2 is a marker of renal allograft rejection and IL-33/ST2 expression may differ according to rejection type. IL-33/ST2 expression was measured in sera and kidney tissues from recipients with acute antibody-mediated rejection (AAMR), acute cell-mediated rejection (ACMR), chronic antibody-mediated rejection (CAMR), and healthy controls.

Molecular Characteristics of the Serological Weak D Phenotype in Koreans.

Serological weak D is a reaction of 2+ or less to anti-D reagent and includes weak D and partial D phenotypes. Although identifying the RhD subtype is important for transfusion safety, serological tests are insufficient for defining the RhD subtype, and molecular tests are needed. To analyze the molecular characteristics of D variants in Koreans to facilitate the formulation of individualized transfusion strategies, molecular tests such as RhD genotyping using real-time polymerase chain reaction (PCR) and partial-D and/or weak-D sequence-specific amplification (SSP) were performed on 105 Korean Rare Blood Program (KRBP) patients exhibiting serological weak D.

Evaluation of LabType-SSO HLA Typing for HLA-A, -B, -C, -DRB1, and -DQB1 loci.

Background: For HLA genotyping, PCR sequence-specific oligonucleotide (SSO) methods using the Luminex platform are widely used. We evaluated the performance of LabType-SSO (One Lambda, USA) in Koreans.

Methods: LabType-SSO were performed on 50 residual DNA samples analyzed by sequence-based typing (SBT) for all HLA-A, -B, -C, -DRB1, and -DQB1 alleles with gene frequency > 0.

Performance evaluation of immunoassay for infectious diseases on the Alinity i system.

Background: Although a diagnosis of infectious diseases is essential for timely treatment, the performance of diagnostic tests has been hardly evaluated due to variable results that are influenced by multiple factors in different conditions. In the present study, the performance of the Alinity i system, which is a newly developed immunoassay to diagnose infectious diseases, was evaluated.

Methods: We evaluated the precision, linearity, correlation, and carryover of 16 analytes (HAV Ab IgG, HBsAg, HBeAg, anti-HBc, anti-HBe, anti-HBs, anti-HCV, HIV Ag/Ab, EBV VCA IgM, EBV VCA IgG, EBV EBNA IgG, CMV IgM, CMV IgG, Toxoplasma IgG, Rubella IgG, and Syphilis TP) of Alinity i by comparison with ARCHITECT i2000 system following the rationale of the Clinical and Laboratory Standards Institute (CLSI).

Umbilical Cord Blood Units Cryopreserved in the Public Cord Blood Bank: A Breakthrough in iPSC Haplobanking?

The use of induced pluripotent stem cells (iPSCs) is an emerging therapeutic option for precision medicine. Cord blood (CB) cells with lower immunogenicity, fewer genomic changes, and persistent epigenetic memory might be ideal candidates for iPSC production. Based on the human leukocyte antigen (HLA) distribution of cord blood units (CBUs) in the public CB bank, we estimated the coverage of the Korean population with HLA-homozygous iPSCs to repurpose cryopreserved CBUs.

Total nucleated cell counts are driving clinician's choice rather than cryopreservation period: Lesson for cord blood banks.

According to the increase in both the number of cryopreserved cord blood (CB) units and the cryopreservation period for each CB unit in the largest public CB bank in Korea, we are pursuing greater efficiency in CB bank management. Thus, we analyzed whether the cryopreservation period has a negative impact on the selection of CB units for CB transplantation (CBT). Until December 2019, 468 CB units were used for transplantation.

Usefulness of the Hematopoietic Stem Cell Donor Pool as a Source of HLA-Homozygous Induced Pluripotent Stem Cells for Haplobanking: Combined Analysis of the Cord Blood Inventory and Bone Marrow Donor Registry.

Induced pluripotent stem cells (iPSCs) have opened up unprecedented opportunities for novel therapeutic options for precision medicine. Hematopoietic stem cell (HSC) donor pools with previously determined HLA types may be ideal sources for iPSC production. Based on the HLA distribution of cryopreserved cord blood units (CBUs) and registered bone marrow (BM) donors, we estimated how much of the Korean population could be covered by HLA-homozygous iPSCs.

Associations of Anti-MHC Class I-related Chain A (MICA) Antibodies with Renal Allograft Outcomes.

The association of anti-MHC class I-related chain A (MICA) and kidney allograft rejection has been reported. However, the associations of antibodies specific to donor MICA (dsMICA) and dsMICA levels with allograft outcome have not been elucidated. From November 2009 to June 2017, 125 sera samples from renal transplantation recipients with no HLA antibodies were screened for MICA antibodies.

Weaning Immunosuppressant in Patients with Failing Kidney Grafts and The Outcomes: A Single-Center Retrospective Cohort Study.

An immunosuppressant weaning protocol in failing allografts has not yet been established. Maintaining immunosuppressants would preserve residual renal function (RRF) and prevent graft intolerance syndrome and sensitization but would increase the risks of infection and malignancy. In this study, graft failure cases after kidney transplantation in a single center were reviewed retrospectively.