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.

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.

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.

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.

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.

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.

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.

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.

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.

Nanoparticle-Based Visual Detection of Amplified DNA for Diagnosis of Hepatitis C Virus.

Rapid, simple, and inexpensive diagnostic point-of-care tests (POCTs) are essential for controlling infectious diseases in resource-limited settings. In this study, we developed a new detection system based on nanoparticle-DNA aggregation (STat aggregation of tagged DNA, STAT-DNA) to yield a visual change that can be easily detected by the naked eye. This simplified optical detection system was applied to detect hepatitis C virus (HCV). Reverse transcription-polymerase chain reaction (RT-PCR) was performed using primers labeled with biotin and digoxigenin. Streptavidin-coated magnetic particles (1 µm) and anti-digoxigenin antibody-coated polystyrene particles (250-350 nm) were added to form aggregates. The limit of detection (LoD) and analytical specificity were analyzed. The STAT-DNA results were compared with those of the standard real-time PCR assay using serum samples from 54 patients with hepatitis C. We achieved visualization of amplified DNA with the naked eye by adding nanoparticles to the PCR mixture without employing centrifugal force, probe addition, incubation, or dilution. The LoD of STAT-DNA was at least 101 IU/mL. STAT-DNA did not show cross-reactivity with eight viral pathogens. The detection using STAT-DNA was consistent with that using standard real-time PCR.

A New Trial to Measure ABO Antibodies Using Complement-Dependent Cytotoxicity.

Background and objectives: The ABO antibody (Ab) titration tests are used in monitoring in ABO-incompatible (ABOi) solid organ transplantation (SOT). However, currently developed ABO Ab tests show Ab binding reactions. This study attempted to measure ABO Ab level using complement-dependent cytotoxicity (CDC). Materials and methods: We studied 93 blood group O serum samples from patients who underwent ABOi SOT from January 2019 to May 2021. Patients' sera were incubated with A1 or B cells and added to a human complement solution. Supernatants were collected after centrifugation, and free hemoglobin (Hb) was measured by spectrophotometry. We converted plasma Hb value to hemolysis (%), which were compared with ABO Ab titer. Results: We found a mild correlation between hemolysis and ABO Ab titers. In simple regression analysis, the correlation coefficients were within 0.3660−0.4968 (p < 0.0001) before transplantation. In multiple linear regression analysis, anti-A hemolysis (%) was higher in immunoglobulin M (IgM) (ß = 12.9) than in immunoglobulin G (IgG) (ß = −3.4) (R2 = 0.5216). Anti-B hemolysis was higher in IgM (ß = 8.7) than in IgG (ß = 0.0) (R2 = 0.5114). There was a large variation in hemolysis within the same Ab titer. Conclusions: CDC can be used in a new trial for ABO Ab measurement. Furthermore, IgM rather than IgG seems to play a significant role in vivo activity, consistent with previous knowledge. Thus, this study may help in the development of the ABO Ab titration supplement test for post-transplant treatment policy establishment and pre-transplant desensitization.

Evaluation and management of platelet transfusion refractoriness.

Platelet transfusion refractoriness (PTR), in which platelet counts do not increase after transfusion, occurs in many patients receiving platelet transfusions. PTR is a clinical condition that can harm patients. The causes of PTR can be divided into two types: immune and non-immune. Most cases of PTR are non-immune. Among immune causes, the most common is human leukocyte antigen (HLA) class I molecules. PTR caused by anti-HLA antibodies is usually managed by transfusing HLA-matched platelets. Therefore, it is important, especially for hemato-oncologists who frequently perform transfusion, to accurately diagnose whether the cause of platelet transfusion failure is alloimmune or non-immunological when determining the treatment direction for the patient. In this review, we discuss the definitions, causes, countermeasures, and prevention methods of PTR.

Detection of anti-B antibodies in a patient with A1B blood group: A case report and literature review.

ABO antibodies occur naturally and usually exist as alloantibodies. They are the most clinically significant in cases of transfusions. However, there are very few reports on auto-anti-A or B. A 58-year-old man visited our hospital for evaluation of an inguinal mass. Blood typing was performed, while preparing the patient for an excisional biopsy. Forward and reverse typing showed a typical AB and A pattern. Results of the direct antiglobulin and unexpected antibody screening tests were negative. The serum did not react with AB3 cells. The biopsy revealed a diffuse large B-cell lymphoma. After completing four cycles of R-CHOP chemotherapy, the patient achieved complete remission. There were no anti-B antibodies found on repeat ABO typing. This report shares our experience on unexpected anti-B antibody findings in a patient with an A1B blood type. To the best of our knowledge, this is the first report of anti-B antibodies in a patient with an A1B blood type in Korea.

The novel HLA-C*06:325 allele identified in a Korean individual awaiting kidney transplantation.

HLA-C*06:325 differs from HLA-C*06:02:01:01 by a non-synonymous nucleotide substitution in codon 145, changing Arginine to Histidine.