The HLA-C*14:152 Allele Was Identified Using a Next-Generation Sequencing Method.

HLA-C*14:152 differs from HLA-C*14:02:01:01 by a non-synonymous nucleotide substitution in exon 5.

Identification of the Novel HLA-DQB1*06:432 Allele by Sequence-Based Typing.

HLA-DQB1*06:432 differs from HLA-DQB1*06:09:01:01 by a nonsynonymous nucleotide substitution in codon 186, changing Valine to Methionine.

Long-term isoagglutinin monitoring after ABO-incompatible kidney transplantation.

OBJECTIVES: This study aimed to evaluate whether a 2-week period of daily isoagglutinin titer testing after ABO-incompatible kidney transplantation (ABOi-KT) is sufficient to ensure successful engraftment and to advocate for an extension of the monitoring duration in specific situations. METHODS: We reviewed patients from January 2022 to December 2023 at Asan Medical Center who underwent therapeutic plasma exchange (TPE) due to elevated ABO antibody titers and suspected acute antibody-mediated rejection (AMR) after ABOi-KT. Data collected included pre- and posttransplantation laboratory results, clinical and procedural information, imaging studies, and needle biopsy results of the renal graft. RESULTS: We encountered 3 cases of acute AMR 2 weeks after transplantation. All cases exhibited simultaneous increases in anti-ABO antibody isoagglutinin titers, creatinine, and C-reactive protein levels. Clinical signs, including fever, suggested possible infection, and renal graft biopsy, confirmed AMR in all cases. Two cases underwent graftectomy, while the third recovered renal function after conservative treatment, including TPE. CONCLUSIONS: Our findings suggest that a 2-week monitoring period for isoagglutinin titers after ABOi-KT may not be sufficient to detect late AMR. Extending the monitoring duration and considering lifelong fresh-frozen plasma transfusion with graft-compatible blood types, along with periodic isoagglutinin titer testing in cases of suspected AMR, may improve long-term graft outcomes.

Genomic full-length sequence of the novel HLA-B*40:540N allele.

The coding sequence of HLA-B*40:540N differs from HLA-B*40:02:01:01 by a non-synonymous nucleotide substitution in exon 3.

The novel HLA-DQA1*03:75 allele identified in a Korean kidney donor.

HLA-DQA1*03:75 differs from HLA-DQA1*03:02:01:01 by a single non-synonymous nucleotide substitution in exon 2.

Genomic full-length sequence of the novel HLA-C*06:364 allele.

HLA-C*06:364 differs from HLA-C*06:02:01:01 by a non-synonymous nucleotide substitution in exon 3.

HLA-DRB1 is associated with cefaclor-induced immediate hypersensitivity.

Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10-8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51-14.09], P < 0.002) and HLA-DRB1∗14:54 (OR 3.86 [95% CI 1.09-13.67], P < 0.002). Conclusion: LIMD1, HLA-DRB1∗04:03 and HLA-DRB1∗14:54 may affect susceptibility to cefaclor induced type I hypersensitivity. Further confirmative studies with a larger patient population should be performed to ascertain the role of HLA-DRB1 and LIMD1 in the development of cefaclor induced hypersensitivity.

Genomic full-length sequence of the novel HLA-B*56:94 allele.

HLA-B*56:94 differs from HLA-B*56:05:01 by two non-synonymous nucleotide substitutions in exon 1 and synonymous nucleotide substitutions in exon 1 and exon 2.

Genomic full-length sequence of the novel HLA-A*02:1100 allele.

HLA-A*02:1100 differs from HLA-A*02:01:01:01 by a single non-synonymous nucleotide substitution in codon 76 of exon 2.

Trends in category and grade for therapeutic plasma exchange in the latest guideline on therapeutic apheresis by the American Society for Apheresis: Hurdles in pursuing evidence-based medicine.

BACKGROUND AND OBJECTIVES: The Writing Committee of American Society for Apheresis released the ninth edition of guidelines for therapeutic apheresis in 2023. Categories have been a part of the guidelines since the first edition, and the grading system was introduced in the fifth edition, with updates in every new edition. In this study, we investigated the category and grade change trends through the latest five editions, focusing on therapeutic plasma exchange, to suggest future directions as part of evidence-based medicine. MATERIALS AND METHODS: Categories and grades for therapeutic plasma exchange (TPE) were collected and analysed from the fifth through ninth editions. We aligned classification changes to the ninth edition's clinical context and compared its categories and grades with those introduced in the guideline. RESULTS: Among 166 total indications in the ninth edition, 118 included TPE procedure, either as a sole treatment or as one of the therapeutic apheresis techniques. The total number of indications changed, but Category III remained predominant throughout the editions. Similarly, Grade 2C consistently emerged as the most prevalent grade. Notably, 24 cases had grade changes. Of the 16 cases with evidence quality changes, the quality weakened in six and improved in 10. Evidence levels were not improved throughout the study period for 102 clinical conditions. CONCLUSION: To address gaps in evidence quality, international collaboration is imperative to establish comprehensive large-scale studies or randomized controlled trials. This will refine the use of therapeutic apheresis, including TPE, to foster evidence-based advancements in clinical practice.

Discovery of the HLA-DQB1*06:465 allele, a variant of HLA-DQB1*06:04:01:01.

HLA-DQB1*06:465 differs from HLA-DQB1*06:04:01:01 by a non-synonymous nucleotide substitution in codon 38.

The novel HLA-C allele, HLA-C*01:02:84 allele, identified in a solid organ transplantation donor.

HLA-C*01:02:84 differs from HLA-C*01:02:01:01 by one synonymous nucleotide substitution in codon 48.

The HLA-B*58:01:43 allele identified in a Korean individual awaiting hematopoietic stem cell transplant.

HLA-B*58:01:43 differs from HLA-B*58:01:01:01 by one synonymous nucleotide substitution in codon 197.

Genomic full-length sequence of the novel HLA-DQB1*04:01:01:04 allele.

The sequence of HLA-DQB1*04:01:01:04 differs from HLA-DQB1*04:01:01:03 by four nucleotide deletion in intron 2.

Clinical significances and distribution of unexpected antibodies found in infants.

INTRODUCTION: The unexpected antibody test is an essential for ensuring the safety of blood transfusions. In infants, different pre-transfusion tests and transfusion strategies are needed due to their immature antigen/antibody system. This study aims to analyze the pattern of unexpected antibodies and their clinical significance in infants. METHODS: A retrospective analysis was conducted on the results of unexpected antibody identification tests performed on infants under one year of age at Asan Medical Center from 1999 to 2022. Patients' unexpected antibody identification test results and clinical information were investigated. The results of unexpected antibody identification and phenotype of each patient's mother were collected. RESULTS: 45 cases of antibody results were studied. 25 cases were found in infants under 4 months of age, and 18 cases (76%) were associated with hemolytic disease of the fetus and newborn (HDFN). The most common unexpected antibody in infants was anti-M (17 cases). There was one case of severe HDFN caused by anti-M. In 10 cases, anti-E and anti-c were found together, and 9 of these cases were associated with HDFN. There were four cases with a history of previous transfusion. CONCLUSIONS: Non-ABO antibodies found in infants showed a different pattern compared to adults. Interpreting unexpected antibody tests in infants, it is important to consider the clinical status of the infant and the test results of the mother, due to possibility of HDFN. To our knowledge, this is the first study to reveal the distribution and clinical significances of unexpected antibodies found in infants in Korea.

Identification of the novel HLA-B*58:138 allele in a Korean individual.

HLA-B*58:138 differs from HLA-B*58:01:01:01 by one nucleotide substitution in exon 3 at codon 145.

Investigation of variables affecting the immunogenicity of blood group antigens using a calculation formula.

Previous studies on the immunogenicity of blood group antigens have utilized a formula incorporating antigen frequencies and relative frequencies of unexpected antibodies to the corresponding antigens. This study was aimed at investigating other variables potentially affecting the estimation of immunogenicity using this formula. We examined the effect of multiple transfusions, as there are more chance for a recipient to receive repeated transfusions rather than only once; the effect of antigen density, which may vary depending on homozygote/heterozygote; and the effect of unreliability of the observed frequency of rare antibodies and antigens. For multiple transfusions, the expected antibody frequency increased as the number of transfusions increased. For antigen density, the immunogenicity was falsely low for the low-prevalence antigen, and this tendency intensified as the effect of antigen density increased. Expected antibody frequencies were significantly affected by the uncertainties caused by estimation of small numbers. This study showed that the effects of various factors on the immunogenicity of blood group antigens depended on the antigen frequency. Estimating the immunogenicity of blood group antigens requires acknowledging the diverse factors that can affect it and interpreting the findings with caution.

Transfusion thresholds: the need for a patient-centered approach in hematologic disorders that require chronic transfusion therapy.

Transfusion is an essential life-sustaining treatment for many patients. However, unnecessary transfusion has been reported to be related to worse patient outcomes. Further, owing to the recent pandemic, blood supply has been more challenging to maintain. Many studies have been conducted to elucidate the optimal transfusion threshold for many clinical conditions, and most suggested that a restrictive transfusion strategy has advantages over a liberal transfusion strategy. Hematologic disorders, which require chronic transfusion in many cases, have not been the main subjects of such studies, and only little evidence is available regarding the optimal transfusion threshold in these patients. According to several recent studies, a liberal transfusion strategy is preferable for patients with hematologic disorders due to their quality of life. A patient-centered approach is needed for proper management of hematologic disorders.

Relative immunogenicity of blood group antigens: First report in a Korean population.

BACKGROUND: The immunogenicity of a blood group antigen is a measure of its likelihood of inducing alloantibodies. Although the immunogenicity of blood group antigens has been analyzed in Caucasian populations, immunogenicity to date has not been analyzed in Asian subjects. The present study therefore evaluated the relative immunogenicity of blood group antigens in a Korean population. STUDY DESIGN AND METHODS: All available data of unexpected antibody identification tests performed at Asan Medical Center between 1997 and 2021 were analyzed. The relative immunogenicity of a blood group antigen relative to K antigen was calculated based on relative numbers of alloantibodies and the probabilities of antigen-negative recipients receiving antigen-positive RBC units. RESULTS: A total of 3898 antibody identification results were included, with 1632 (41.9 %) from male patients. The ranking of antigen immunogenicity was: E > c > e > C > K > Jk(a) > Lu(a) > S > Fy(a) > Fy(b) > Jk(b) > Di(b) > Di(a) in the total population and E > c > e > C > Jk(a) > Fy(a) > Fy(b) > S > K > Lu(a) > Jk(b) > Di(b) > Di(a) in male patients. DISCUSSION: The rank order of immunogenicity for blood group antigens in this study provides information about relative immunogenecity in Koreans. These findings also provide supporting evidence regarding antigen selection for extended antigen-matched transfusions in recipients of multiple transfusions.

Identification of the novel HLA-A*11:423 allele by sequencing-based typing.

HLA-A*11:423 differs from HLA-A*11:01:01:01 by a non-synonymous nucleotide substitution in codon 170, changing Arginine to Lysine.