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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.

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. This article is protected by copyright. All rights reserved.

Background Recent studies have successfully implemented next-generation sequencing (NGS) in HLA typing. We performed HLA NGS in a Korean population to estimate HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies up to an 8-digit resolution, which might be useful for an extended application of HLA results. Methods A total of 128 samples collected from healthy unrelated Korean adults, previously subjected to Sanger sequencing for 6-digit HLA analysis, were used. NGS was performed for HLA-A, -B, -C, and -DRB1 using the AllType NGS kit (One Lambda, West Hills, CA, USA), Ion Torrent S5 platform (Thermo Fisher Scientific, Waltham, MA, USA), and Type Steam Visual NGS analysis software (One Lambda). Results Eight HLA alleles showed frequencies of ≥10% in the Korean population, namely, A*24:02:01:01 (19.5%), A*33:03:01 (15.6%), A*02:01:01:01 (14.5%), A*11:01:01:01 (13.3%), B*15:01:01:01 (10.2%), C*01:02:01 (19.9%), C*03:04:01:02 (11.3%), and DRB1*09:01:02 (10.2%). Nine previous 6-digit HLA alleles were further identified as two or more 8-digit HLA alleles. Of these, eight alleles (A*24:02:01, B*35:01:01, B*40:01:02, B*55:02:01, B*58:01:01, C*03:02:02, C*07:02:01, and DRB1*07:01:01) were identified as two 8-digit HLA alleles, and one allele (B*51:01:01) was identified as three 8-digit HLA alleles. The most frequent four-loci haplotype was HLA-A*33:03:01-B*44:03:01:01-C*14:03-DRB1*13:02:01. Conclusions We identified 8-digit HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies in a healthy Korean population using NGS. These new data can be used as a representative Korean data for further disease-related HLA type analysis.

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.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.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.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.

Background HLA-DQ typing in deceased donors is not mandatory in Korea. Therefore, when patients develop DQ antibodies after kidney transplantation (KT) from deceased donor, it is impossible to determine whether they are donor-specific antibodies (DSA). We developed DQ prediction programs for the HLA gene and evaluated their clinical utility. Methods Two HLA-DQ prediction programs were developed: one based on Lewontin's linkage disequilibrium (LD) and haplotype frequency and the other on an artificial neural network (ANN). Low-resolution HLA-A, -B, -DR, and -DQ typing data of 5,603 Korean patients were analyzed in terms of haplotype frequency and used to develop an ANN DQ prediction program. Predicted DQ (pDQ) genotype accuracy was analyzed using the typed DQ data of 403 patients. pDQ DSA agreement, sensitivity, specificity, and false-negative rate was evaluated using 1,970 single-antigen bead assays performed on 885 KT recipients. The clinical significance of DQ and pDQ DSA was evaluated in 411 KT recipients. Results pDQ genotype accuracies were 75.4% (LD algorithm) and 75.7% (ANN). When the second most likely pDQ (LD algorithm) was also considered, the genotype accuracy increased to 92.6%. pDQ DSA (LD algorithm) agreement, sensitivity, specificity, and false-negative rate were 97.5%, 97.3%, 98.6%, and 2.4%, respectively. The antibody-mediated rejection treatment frequency was significantly higher in DQ or pDQ DSA-positive patients than in DQ or pDQ DSA-negative patients (P

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.

Objective We compared the clinical outcomes of recipients of ABO-incompatible (ABOi) kidney transplantation (KT) according to the blood group of the plasma transfused. Materials and Methods We retrospectively analyzed the data of 60 recipients of ABOi-KT with blood type O and A or B donors. Demographic and clinical characteristics were compared between 2 groups of recipients: 1 group received AB plasma regardless of the donor’s blood type (n = 30), and the other group received donor-type plasma (n = 30). Results There were no significant differences between the groups in terms of demographic characteristics. Transfusion of donor-type plasma was noninferior to transfusion of type AB plasma in terms of both rejection-free survival and rejection rate (P = .455, P = .335). Conclusion There was no significant prognostic difference between the 2 groups. In terms of blood supply and inventory management, we suggest that the blood group of the plasma should match the donor’s type.

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.

Objective We designed a study to compare the efficacy of cryoprecipitate-reduced plasma (CRP) and fresh frozen plasma (FFP), at the level of individual sessions, for treating refractory thrombotic microangiopathy (TMA) with therapeutic plasma exchange (TPE). Materials and Methods Platelet counts (× 10³/μL) and lactate dehydrogenase (LD; IU/L) levels were measured before and after each session. We compared the mean-percentage and absolute changes in platelet count and LD after each TPE session. Results The data from 33 patients treated for TMA between 2009 and 2018 were collected for this study. Both absolute and percentage increases in the platelet count were statistically significant (P = .003 and P = .011, respectively) when CRP was used. However, when patients were divided into subgroups according to specific diagnosis, no significant differences were found among the groups, except in terms of the absolute platelet count increase in the thrombotic thrombocytopenic purpura group (P Conclusion The platelet count increase was higher when patients received CRP than when they received FFP. We found that CRP may be a rescue option for patients with refractory TMA.

Objectives Rh(D)-incompatible (Rh-i) solid organ transplantations are not considered for organ matching, but no consensus guidelines exist regarding the need for anti-D immunoglobulin (RhIG) prophylaxis. Methods We reviewed 35 Rh(D)-negative patients who had received Rh-i solid organ transplantation. We divided the patients into a RhIG-administered group and a nonadministered group. All patients also underwent an antibody screening test to assess Rh alloimmunization. Graft function was monitored with serum creatinine or bilirubin and kidney or liver biopsy whenever a rejection was suspected. Overall survival was also assessed. Results The median (range) age of transplant recipients was 48.5 (4-69) years, and 73.5% of patients were male. Median (range) follow-up time after transplantation was 60 (2-246) months. In the RhIG nonadministered group (n = 16), anti-D was not detected in any of the patients. More rejection episodes occurred in the RhIG-administered group among those undergoing kidney transplant (P = .0278). Conclusions The low rate of Rh(D) alloimmunization is associated with the immunosuppressive state of the patients. RhIG prophylaxis seems to have no clinical benefit in Rh-i solid organ transplantation.

Introduction Chimerism is defined as coexistence of different cell lines in an individual. 46,XX/46,XY chimerism is very rare and exhibits broad range of clinical phenotypes. Most cases are detected at infancy or younger age due to disorders of sex development, while phenotypically normal cases are incidentally discovered through abnormal blood grouping results or multiple genotypes in HLA. Objective Aim was to determine the genetic expression of numerous HLA alleles detected in phenotypically normal 46,XX/46,XY chimerism. Materials and methods A patient was admitted for lung transplantation due to end-stage pulmonary disease. Pre-transplantation work-up included blood group typing and HLA DNA typing analyses. Peripheral blood and hair follicle specimens were used to confirm unusual tri-allelic results by high-resolution PCR-SBT. Cytogenetic analyses of karyotyping, FISH and chromosomal microarray were done. Flowcytometry crossmatch analysis was conducted using lymphocytes and anti-HLA sera defined by Luminex panel reactive antibody test (One Lambda, Inc., Canoga Park, CA), to determine antigen expression of HLA alleles. Results 46,XX/46,XY chimerism was confirmed through series of cytogenetic analyses. HLA typing of the patient revealed three alleles from HLA-A, -B and -DRB1 loci. Antigen expression of all 3 HLA alleles was confirmed by flow cytometry crossmatch. Discussion A case of normal phenotype 46,XX/46,XY chimerism was detected for the first time in Korean patient admitted for lung transplantation. Cytogenetic results were confirmatory for chimerism and HLA typing using PCR-SBT method was able to detect the presence of 3 HLA alleles. Flowcytometry crossmatch was proven sensitive for detecting antigen expression of different cell lines of small proportions.

Affordable point-of-care (POC) CD4 + T lymphocyte counting techniques have been developed as alternatives to flow cytometry-based instruments caring for patients with human immunodeficiency virus (HIV)-1. However, POC CD4 enumeration technologies can be inaccurate. Here, we developed a microparticle-based visual detector of CD4 + T lymphocytes (ImmunoSpin) using microparticles conjugated with anti-CD4 antibodies, independent of microfluidic or fluorescence detection systems. Visual enumeration of CD4 + T cells under conventional light microscope was accurate compared to flow cytometry. Microparticle-tagged CD4 + T cells were well-recognized under a light microscope. ImmunoSpin showed very good precision (coefficients of variation of ImmunoSpin were ≤ 10%) and high correlation with clinical-grade flow cytometry for the enumeration of CD4 + T cells (y = 0.4232 + 0.9485 × for the %CD4 + T cell count, R2 = 0.99). At thresholds of 200 and 350 cells/µL, there was no misclassification of the ImmunoSpin system compared to the reference flow cytometry. ImmunoSpin showed clear differential classification of CD4 + T lymphocytes from granulocytes and monocytes. Because non-fluorescence microparticle-tags and cytospin slides are used in ImmunoSpin, they can be applied to an automatic digital image analyzer. Slide preparation allows long-term storage, no analysis time limitations, and image transfer in remote areas. Graphical abstract

Background Criteria for selection of FFP blood type has not been clearly established and use of group AB plasma is preferred by numerous transplantation protocols. Aims This study assesses the safety and efficacy of alternative group A or B plasma in ABO incompatible solid organ transplantation. Materials & methods Alternative use of group A or B plasma (incompatible plasma) was inevitable during the shortage of group AB plasma. Experience from select number of patients during the period of extreme group AB plasma shortage is described. Results The result of alternative use of group A or B plasma was within expectation, showing effective reduction of isoagglutinin titers for pre-operative desensitization and efficacy for treatment of post-operative patients. No immediate hemolytic transfusion reaction was reported. Discussion While validation in a larger cohort of patients is necessary, our limited experience have shown satisfactory clinical outcomes without adverse events. Conclusions Use of incompatible group A or B plasma is a viable option when group AB plasma is limited.

HLA-DQB1*03:457 differs from HLA-DQB1*03:02:01:01 by a non-synonymous nucleotide substitution in codon 95, changing valine to glutamic acid.

The novel HLA-C*03:539 allele differs from HLA-C*03:04:01:01 by one nucleotide substitution at codon 26.

The HLA-DPA1*02:02:08 allele differs from HLA-DPA1*02:02:02:01 by a synonymous nucleotide substitution at codon 194.

Disease progression (DP) in interstitial lung disease (ILD) is variable and difficult to predict. In previous reports, serum Krebs von den Lungen-6 (KL-6) was suggested to be useful in diagnosing and predicting survival in ILD. The aim of our study was to investigate the usefulness of serum KL-6 as a predictor of DP in ILD. Clinical data of 199 patients with ILD (idiopathic pulmonary fibrosis: 22.8%) were prospectively collected and serum KL-6 levels were measured. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, acute exacerbation, or death during follow-up. The median follow-up period was 11.1 months. The mean age of the subjects was 62.2 years, and 59.8% were male. DP occurred in 21.6% of patients. The progressed group showed lower FVC, lower diffusing capacity for carbon monoxide, lower the minimum oxygen saturation during the 6-minute walk test, higher fibrosis scores on high-resolution computed tomography, and higher KL-6 levels (826.3 vs. 629.0 U/mL; p < 0.001) than those of the non-progressed group. In receiver operating characteristic curve analysis, serum KL-6 levels were a significant predictor of DP in ILD (area under the curve = 0.629, p = 0.009, and the optimal cut-off level was 811 U/mL). In multivariable Cox analysis, high serum KL-6 levels (≥ 800 U/mL) were only independently associated with DP in ILD (HR 2.689, 95% CI 1.445–5.004, P = 0.002). Serum KL-6 levels might be useful to predict DP in patients with ILD.