Allele and Haplotype Frequencies of HLA-A, -B, -C, and -DRB1 Genes in 3,750 Cord Blood Units From a Kinh Vietnamese Population.

The frequencies and diversities of human leukocyte antigen (HLA) alleles and haplotypes are representative of ethnicities. Matching HLA alleles is essential for many clinical applications, including blood transfusion, stem cell transplantation, and tissue/organ transplantation. To date, the information about the frequencies and distributions of HLA alleles and haplotypes among the Kinh Vietnamese population is limited because of the small sample size. In this study, more than 3,750 cord blood units from individuals belonging to the Kinh Vietnamese population were genotyped using PCR sequence-specific oligonucleotide (PCR-SSO) for HLA testing. The results of the study demonstrated that the most frequently occurring HLA-A, -B, -C, and -DRB1 alleles were A*11:01 (25%), A*24:02 (12.3%), A*02:01 (11.2); A*03:03 (8.95%), A*02:03 (7.81%), A*29:01 (7.03%); B*15:02 (15.1%), B*46:01 (10.7%), B*58:01 (7.65%), B*38:02 (7.29%); C*08:01 (17.2), C*07:02 (16.2%), C*01:02 (15.2), C*03:02 (8.3%), C*15:05 (6.13); DRB1*12:02 (31.0%), DRB1*09:01 (10.47%), DRB1*15:02 (7.54%); DRB1*07:01 (6.68%), DRB1*10:01 (6.63%), respectively, with the highest allele diversity level observed in locus B (93 alleles). The most frequent haplotypes of two-locus combinations of HLA-A-B, HLA-A-C, HLA-A-DRB1, HLA-B-C, HLA-B-DRB1, and HLA-C-DRB1 haplotypes were A*11:01-B*15:02 (7.63%), A*11:01-C*08:01 (7.98%), A*11:01-DRB1*12:02 (10.56%), B*15:02-C*08:01 (14.0%), B*15:02-DRB1*12:02 (10.47%), and C*08:01-DRB1*12:02 (11.38%), respectively. In addition, the most frequent haplotypes of three- and four-locus sets of HLA-A-B-C, HLA-A-B-DRB1, HLA-A-C-DRB1, HLA-B-C-DRB1, and HLA-A-B-C-DRB1 were A*11:01-B*15:02-C*08:01 (7.57%), A*11:01-B*15:02-DRB1*12:02 (5.39%), A*11:01-C*08:01-DRB1*12:02 (5.54%), B*15:02-C*08:01-DRB1*12:02 (10.21%), and A*11:01-B*15:02-C*08:01-DRB1*12:02 (5.45%), respectively. This study provides critical information on the frequencies and distributions of HLA alleles and haplotypes in the Kinh Vietnamese population, accounting for more than 85% of Vietnamese citizens. It paves the way to establish an umbilical cord blood bank for cord blood transplantation programs in Vietnam.

Evaluation of three different laboratory methods to detect preformed human leukocyte antigen antibodies in a South African kidney transplant population.

BACKGROUND: Anti-human leukocyte antigen antibodies (anti-HLA) play a crucial role in graft. Detection of anti-HLA, both pre- and post-transplant is a crucial investigation in clinical organ transplantation. OBJECTIVES: Three methodologies for the detection of lymphocytotoxic antibodies were compared to establish which of these is best suited to optimise pre-transplant donor-recipient matching. METHODS: Serum samples from 15 renal transplant patients were tested for the presence of anti-HLA by i) cytotoxic-dependent cross-match (CDCXM), ii) flow cytometric cross-match (FCXM) and iii) Luminex-based donor specific antibody cross-match (DSAXM) method, Confirmatory tests for the presence of preformed HLA antibodies were tested using Luminex methodology. RESULTS: Two (13%) of the 15 patients had positive HLA Class I antibodies (Ab) using all 3 methods. An additional 2 HLA Class I Ab were identified with FCXM/CDCXM. DSAXM identified 1 HLA Class I positive, not indicated by CDCXM/FCXM.High HLA Class II positivity (40%), identified by CDCXM, while DSAXM and FCXM identified two and one patients, respectively. CDCXM produced 4 false-positive results confirmed by lymphocyte single antigen (LSA) assay. CONCLUSIONS: The DSAXM method appears to add value in pre-transplantation screening to identify pre-sensitised patients that may not reject the donor graft due to the absence of donor-specific antibodies.

A case report of prenatal diagnosis of fetal alloimmune thrombocytopenia: A CARE-compliant article.

RATIONALE: Fetal alloimmune thrombocytopenia (FAIT) is a serious life-threatening disease caused by platelet-antigen incompatibility between the mother and fetus. FAIT can lead to fetal thrombocytopenia, intracranial hemorrhage (ICH), fetal death and severe neurological disorders after birth. Noninvasive prenatal diagnosis technology has not been widely used in China, and thus few cases of FAIT can be diagnosed prenatally. In this study, we report a case of prenatal diagnosis and treatment of FAIT. PATIENT CONCERNS: A 29-year-old female was admitted at 32 weeks' gestational age (GA). Fetal ultrasound at 32 weeks' GA showed a hemorrhagic focus area in the left lateral ventricle and the sign of severe fetal anemia. Hence, fetal umbilical cord puncture was ordered to identify the etiology. DIAGNOSES: The fetal cord blood test revealed a normal hemoglobin level but severe fetal thrombocytopenia (platelet count, 23 × 109/L). Antibodies of human platelet antigens and human leukocyte antigens between mother and fetus were positive, and thus the diagnosis of FAIT was confirmed. INTERVENTIONS: The patient refused intravenous immunoglobulin (IVIG) therapy owing to financial consideration. She was treated with dexamethasone acetate tablets (Xianju Company, China) 0.75 mg twice a day until delivery and cesarean section was performed at 34 weeks' GA. The newborn received postnatal anti-platelet antibody treatment. OUTCOMES: The platelet count of the newborn progressively decreased until the third day after birth and it increased to normal level after postnatal treatment. The neonatal cerebral ultrasound showed the area of hemorrhage was in the process of absorption. During the postnatal one-year follow-up, the neonate showed normal developmental milestones and had no abnormal signs of neurological symptoms. LESSONS: For FAIT, the fetal umbilical cord puncture can be carried out by skilled fetal medical teams. Dexamethasone acetate tablets can be an alternative choice for patients from underdeveloped areas.

No strong HLA association with MOG antibody disease in the UK population.

Improvements in assays for detecting serum antibodies against myelin oligodendrocyte glycoprotein (MOG) have led to the appreciation of MOG-antibody-associated disease (MOGAD) as a novel disorder. However, much remains unknown about its etiology. We performed human leukocyte antigen (HLA) analysis in 82 MOGAD patients of European ancestry in the UK population. No HLA class II associations were observed, thus questioning the mechanism of anti-MOG antibody generation. A weak protective association of HLA-C*03:04 was observed (OR = 0.26, 95% CI = 0.10-0.71, pc  = 0.013), suggesting a need for continued efforts to better understand MOGAD genetics and pathophysiology.

Rebound and overshoot of donor-specific antibodies to human leukocyte antigens (HLA) during desensitization with plasma exchanges in hematopoietic progenitor cell transplantation: A case report.

BACKGROUND: Donor-specific antibodies (DSA) to HLA have been associated with graft loss in hematopoietic progenitor cell (HPC) transplantation. Limited data associate therapeutic plasma exchange (TPE) with desensitization and successful engraftment. We report an attempt of desensitization and observed overshooting of DSA during transplantation. CASE REPORT AND RESULTS: A 27-year-old female with cutaneous T cell lymphoma was scheduled for HPC transplantation from her HLA-haploidentical half-sister, who carried the HLA-DRB1*13:03:01 allele. The patient had the corresponding DSA. Lacking an alternative donor option at the time, we attempted a desensitization approach by immunosuppression with tacrolimus and mycophenolate mofetil (MMF). Unexpectedly, DSA increased from a mean fluorescence intensity (MFI) of 1835 on day -63 to 9008 on day -7. The MFI increased further during 3 TPE procedures and intravenous immunoglobulin (IVIG) until day -1. After transplantation, the DSA remained elevated despite 2 more TPE/IVIG procedures and graft-versus-host disease prophylaxis with high-dose cyclophosphamide, sirolimus, and MMF. Flow cytometric crossmatch, initially negative, turned positive after transplantation. Primary graft failure occurred and was attributed to antibody-mediated rejection. A second transplantation from a 7/8 HLA-matched unrelated donor, not carrying DRB1*13:03 allele, resulted in successful engraftment. CONCLUSION: Unexpected and rapid increases of a DSA can occur despite the use of current desensitization approaches. This is problematic when conditioning has already started, as such increases are unlikely to be overcome by TPE or other interventions for desensitization. Overshoot of DSA in HPC transplantation has rarely been reported. Its cause remains unclear and can include underlying disease, immunotherapy, chemotherapy, or TPE.

The Role of Immunogenetics in COVID-19.

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies. In the frenetic look for universally shared treatment plans, those genetic variants that are common to other diseases/models may also help in addressing future research in terms of drug repurposing. In this paper, we discuss the most recent updates about the role of immunogenetics in determining the susceptibility to and the history of SARS-CoV-2 infection. We propose a narrative review of available data, speculating about lessons that we have learnt from other viral infections and immunosenescence, and discussing what kind of aspects of research should be deepened in order to improve our knowledge of how host genetic variability impacts the outcome for COVID-19 patients.

Interpretation of the HLA epitopes-Continuous dilution method for detection of high-titer IgG HLA antibody.

BACKGROUND: The presence or absence of human leukocyte antigen (HLA) antibodies, especially the strength of donor-specific HLA antibodies (DSAs), has important roles in clinical evaluation and diagnostic decision-making for solid-organ transplantation. Dilution patterns help to give a new sight of HLA epitopes. "Epitope matching" is likely to lower the risk of developing DSA and increase the likelihood of matching a compatible donor. METHODS: We collected data evaluating HLA antibodies with a titration study using mean fluorescence intensity. RESULTS: Diluting the serum of recipients can reduce potential inhibitory effects, accurately evaluate the intensity of donor-specific HLA antibodies, and guide surgeons to take or not take intervention measures. Dilution patterns also help to give a new sight of HLA epitopes. CONCLUSION: We believe that from the viewpoint of HLA antibodies, the dilution model can provide new tools and insights for the study of HLA epitopes.

C1q-binding DSA and allograft outcomes in pediatric kidney transplant recipients.

Donor-specific antibody (DSA) is an independent risk factor for antibody-mediated rejection (ABMR) and graft loss. The C1q assay differentiates complement from non-complement-binding DSA and C1q-binding DSA may lead to poor allograft survival. Our aim was to characterize the type of DSA seen in pediatric kidney transplant recipients and to determine whether complement binding DSA was associated with inferior graft survival.This was a single-center retrospective study of 48 children who were transplanted between 2009 and 2016. DSA were monitored using Luminex single antigen beads. A negative crossmatch was required to proceed with transplantation. The median follow-up time was 4.9 (3.4, 7.9) years. The median age was 12 (5.7, 15.4) years. DSA developed in 27/48 (56.3%), while C1q-binding DSA developed in 17/27 (63%). There were no significant differences between DSA negative, C1q-binding DSA, and C1q negative DSA, with regard to the number of HLA-ABDR (P  =  .09) or HLA-DQ mismatches alone (P  =  .16). For both C1q negative and C1q-binding DSA, DQ was the most common target of the DSA (19/27; 70.4%). C1q-binding DSA was associated with a significantly higher frequency of biopsy proven rejection (76.5%) when compared to C1q negative (10%) and DSA negative (14.3%); P  =  .001. Graft loss was seen in 6 (12.5%), all of whom had C1q-binding DSA (P  =  .004). C1q-binding DSA was most commonly directed to DQ antigens. C1q-binding DSA was associated with increased rejection and graft loss. Monitoring for C1q-binding DSA may risk stratify recipients and guide physician management.

The utility of second single antigen bead assay: Clearing the water or stirring up mud?

Though solid-phase single antigen bead (SAB) testing has provided major advances to the HLA community and organ allocation, it has not been without limitations. In particular, false-positive reactions lead to interpretative challenges and the potential to preclude a transplant if the corresponding antigens are deemed unacceptable. Two different vendor platforms are commercially available for SAB testing, one more recent than the other. The aim herein was to assess the benefit of using the newer SAB platform in situations where the primary platform yielded suspicious (specifically, false positive) reactions. Therefore, 42 serum samples with commonly encountered false-positive patterns observed in our laboratory were tested with the newer platform. Cases were classified as resolved, equivalent, or divergent based on whether the second platform produced no reactivity, the same pattern, or a distinctly different pattern compared to the primary platform, respectively. Approximately 33% of cases were resolved, 46% were equivalent, and 21% were divergent. The project revealed advantages of adding a second SAB platform to the laboratory's test menu including resolving challenging samples and including broader coverage of different alleles and unique class II alpha/beta subunit combinations. However, the challenges of validating, maintaining, and billing for another test method in the laboratory may be barriers to routine use.

ACE2 and TMPRSS2 expression by clinical, HLA, immune, and microbial correlates across 34 human cancers and matched normal tissues: implications for SARS-CoV-2 COVID-19.

BACKGROUND: Pandemic COVID-19 by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) infection is facilitated by the ACE2 receptor and protease TMPRSS2. Modestly sized case series have described clinical factors associated with COVID-19, while ACE2 and TMPRSS2 expression analyses have been described in some cell types. Patients with cancer may have worse outcomes to COVID-19. METHODS: We performed an integrated study of ACE2 and TMPRSS2 gene expression across and within organ systems, by normal versus tumor, across several existing databases (The Cancer Genome Atlas, Census of Immune Single Cell Expression Atlas, The Human Cell Landscape, and more). We correlated gene expression with clinical factors (including but not limited to age, gender, race, body mass index, and smoking history), HLA genotype, immune gene expression patterns, cell subsets, and single-cell sequencing as well as commensal microbiome. RESULTS: Matched normal tissues generally display higher ACE2 and TMPRSS2 expression compared with cancer, with normal and tumor from digestive organs expressing the highest levels. No clinical factors were consistently identified to be significantly associated with gene expression levels though outlier organ systems were observed for some factors. Similarly, no HLA genotypes were consistently associated with gene expression levels. Strong correlations were observed between ACE2 expression levels and multiple immune gene signatures including interferon-stimulated genes and the T cell-inflamed phenotype as well as inverse associations with angiogenesis and transforming growth factor-ß signatures. ACE2 positively correlated with macrophage subsets across tumor types. TMPRSS2 was less associated with immune gene expression but was strongly associated with epithelial cell abundance. Single-cell sequencing analysis across nine independent studies demonstrated little to no ACE2 or TMPRSS2 expression in lymphocytes or macrophages. ACE2 and TMPRSS2 gene expression associated with commensal microbiota in matched normal tissues particularly from colorectal cancers, with distinct bacterial populations showing strong associations. CONCLUSIONS: We performed a large-scale integration of ACE2 and TMPRSS2 gene expression across clinical, genetic, and microbiome domains. We identify novel associations with the microbiota and confirm host immunity associations with gene expression. We suggest caution in interpretation regarding genetic associations with ACE2 expression suggested from smaller case series.

Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulated radiation therapy or stereotactic ablative body radiotherapy.

BACKGROUND: In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modulates the immune system. PATIENTS AND METHODS: RT-qPCR, flow cytometry, metabolomics, and antibody arrays were used to monitor a panel of stress- and immune-related parameters before RT, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and 3 weeks later in the blood of IMRT (N = 4) or SABR (N = 4) patients. Effect size analysis was used for comparison of results at different timepoints. RESULTS: Several parameters were found to be differentially modulated in IMRT and SABR patients: the expression of TGFB1, IL1B, and CCL3 genes; the expression of HLA-DR on circulating monocytes; the abundance and ratio of phosphatidylcholine and lysophosphatidylcholine metabolites in plasma. More immune modulators in plasma were modulated during IMRT than SABR, with only two common proteins, namely GDF-15 and Tim­3. CONCLUSION: Locally delivered RT induces systemic modulation of the immune system in prostate adenocarcinoma patients. IMRT and SABR appear to specifically affect distinct immune components.

[A case of sporadic late-onset nemaline myopathy associated with myasthenia gravis positive for anti-titin antibody and anti-Kv1.4 antibody].

A 66-year-old woman who had myasthenia gravis (MG) admitted for type II respiratory failure and right heart failure. Although she had neither ptosis, eye movement disorder, nor diplopia, she had orbital muscles weakness, reduction of gag reflex, dysarthria, dysphagia, and mild proximal muscle weakness. Blood tests showed anti-striated muscle antibodies (anti-titin antibody and anti-Kv1.4 antibody). A muscle biopsy of the left biceps showed a marked variation in fiber size, mild mononuclear cell infiltration was seen surrounding blood vessels in perimysium and nemaline bodies in some fibers. Immunohistochemical stains showed many muscle fibers express HLA-ABC. The patient was diagnosed as sporadic late-onset nemaline myopathy (SLONM) with MG, and treated by tacrolimus. After treatment, her respiratory function gradually improved and she discharged. In the case of atypical MG, measurement of anti-striated muscle antibody or muscle biopsy should be considered.

Human Leukocyte Antigen Class I Antibodies and Response to Platelet Transfusion in Patients Undergoing Liver Transplantation.

BACKGROUND: Patients undergoing liver transplantation (LT) frequently receive platelet transfusion (PLT) to minimize their risk of hemorrhage. Alloimmunization to platelets may lead to refractoriness to PLT. Data on the implications of platelet alloimmunization in patients undergoing LT remain limited. We examined the effect of human leukocyte antigen class I (HLA-I) antibodies on PLT refractoriness and short-term outcomes after LT. METHODS: Peritransplant clinical and PLT factors were reviewed for all adult liver or simultaneous liver-kidney transplantations from 2012 to 2017. Sensitized patients (SE) with pretransplant HLA-I calculated panel-reactive antibody ≥20% were compared with unsensitized patients (US) with calculated panel-reactive antibody <20%. The mean follow-up was 21.4 mo. RESULTS: Alloimmunization was observed in 39% of the study cohort. SE (n = 28) received 272 PLTs, and US (n = 44) received 246 PLTs. History of pregnancy was higher among SE than US (P < 0.01); otherwise, both groups had similar clinical characteristics. SE had higher rates of PLT refractoriness (66% versus 47%; P < 0.01) than US. The mean platelet corrected count increment was lower among SE compared with US up to 100 min after PLT (P < 0.05). Alloimmunization and simultaneous liver-kidney transplantation independently predicted refractoriness on multivariate logistic regression (P < 0.05). Early allograft rejection and patient survival rates were comparable for both groups. CONCLUSIONS: LT patients experienced high rates of HLA-I alloimmunization and PLT refractoriness. SE had higher rates of refractoriness and lower mean corrected count increment after transfusion compared with US. Our study suggests that further research to evaluate the utility of HLA-matched PLTs in HLA-I alloimmunized LT patients is warranted.

Improved access to better HLA-matched hematopoietic cells for allogeneic transplant: analysis of donors and cord blood units selected for Canadian patients in 2018.

BACKGROUND: Patients undergoing hematopoietic cell transplantation (HCT) often require use of an unrelated donor or cord blood unit (CBU). An understanding of evolving practices in graft selection is needed for optimization of donor recruitment and cord blood collection. STUDY DESIGN AND METHODS: Each donor workup (WU) requested in 2018 involving a Canadian (CDN) patient and unique donor product or CBU was reviewed (n = 598). Degree of HLA match; product origin (domestic or international [INT]); and non-HLA factors including donor age, sex, cytomegalovirus (CMV), and ABO compatibility were analyzed for WUs that proceeded to transplant (n = 414). We also analyzed changes compared to a similar analysis performed in 2013. RESULTS: The majority of transplants used matched unrelated donors (MUDs; n = 323; 78%) and were most often young (≤35 years), male, INT donors (n = 136). The proportion of transplants involving MUDs, as opposed to mismatched unrelated donors or CBUs, increased by 12.4% compared with 2013. When young, male, CDN MUDs were identified in patient search reports but not selected, CMV mismatching and ABO incompatibility were most likely to have influenced the decision to use an INT MUD. Consistent with global trends, CBU transplants decreased compared to 2013; however, the degree of HLA matching improved significantly, and 27% of transplanted CBUs were procured from the Canadian Blood Services Cord Blood Bank. CONCLUSIONS: Access to MUDs and better HLA-matched CBUs by CDN patients has increased since 2013. Ongoing recruitment of young registrants and cord blood donors with diverse HLA haplotypes will support selection of donors with optimal non-HLA characteristics.

Increased Calculated Panel Reactive Antigen Is Associated With Increased Waitlist Time and Mortality in Lung Transplantation.

BACKGROUND: Sensitized candidates with unacceptable antigens are a group that demands special attention in organ transplantation. Calculated panel reactive antigen (cPRA) is not used to modify allocation priorities in lung transplantation. The impact of cPRA on waiting list time and mortality is unknown. METHODS: We performed a retrospective review of candidates for lung transplantation listed from May 2005 to 2018. Data from the Organ Procurement and Transplantation Network/United Network for Organ Sharing STAR (Standard Analysis and Research) dataset was paired with additional unacceptable human leukocyte antigen (UA-HLA) data, which were used to calculate the listing cPRA. Candidates were stratified based on the lack of UA-HLAs or cPRA level for candidates with unacceptable antigens reported. Unadjusted competing risks and adjusted subdistribution hazard models were fit. RESULTS: A total of 29,085 candidates met inclusion criteria for analysis. Of these, 23,562 (81%) with no UA-HLAs, 3472 (11.9%) with a cPRA less than 50, and 2051 with a cPRA greater than or equal to 50 (7.1%). On adjusted analysis, a cPRA greater than or equal to 50 was independently associated with increased waitlist mortality at 1 year (hazard ratio, 1.71; 95% confidence interval, 1.55-1.88; P < .001) and decreased rate of transplantation (71.9% vs 69.5% vs 44.4%; P < .001). Furthermore, patients with a cPRA greater than or equal to 50 had a longer waitlist time compared with a cPRA less than 50 and no UA-HLA candidates (mean 293.69 days vs 162.38 days and 143.26 days, respectively; P < .001). However, once transplanted, posttransplant survival among the cohorts was similar. CONCLUSIONS: Further evaluation of organ allocation with consideration of a candidate's cPRA may be warranted in order to optimize equity in access to transplants.

Flow cytometry evaluation of infection-related biomarkers in febrile subjects in the emergency department.

Aim: In an Emergency Department (ED), the etiological identification of infected subjects is essential. 13 infection-related biomarkers were assessed using a new flow cytometry procedure. Materials & methods: If subjects presented with febrile symptoms at the ED, 13 biomarkers' levels, including CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), were tested and compared with clinical records. Results: Among 50 subjects, 78% had bacterial infections and 8% had viral infections. nCD64 showed 82% sensitivity and 91% specificity for identifying subjects with bacterial infections. mCD169, HLA-ABC ratio and HLA-DR on monocytes had high values in subjects with viral infections. Conclusion: Biomarkers showed promising performances to improve the ED's infectious stratification.

Ensuring HLA-matched platelet support requires an ethnic diverse donor population.

BACKGROUND: Patients refractory for platelet transfusions benefit from human leukocyte antigen (HLA)-matched platelet transfusions. Differences in ethnic background of patients and donors could hamper the availability of sufficient numbers of HLA-matched donors for all patients. We evaluated our HLA-matched donor program and explored the role of ethnic background of patients related to the number of available donors. METHODS: We performed a cohort study among consecutive patients who received HLA-matched platelet concentrates in the Netherlands between 1994 and 2017. The number of available matched donors was determined per patient. Haplotypes were constructed from genotypes with computer software (PyPop). Based on haplotypes, HaploStats, an algorithm from the National Marrow Donor Program, was used to assess the most likely ethnic background for patients with 5 or fewer and 30 or more donors. RESULTS: HLA typing was available for 19,478 donors in September 2017. A total of 1206 patients received 12,350 HLA-matched transfusions. A median of 83 (interquartile range, 18-266) donors were available per patient. For 95 (10.3%) patients, 5 or fewer donors were available. These patients were more likely to have an African American background, whereas patients with 30 or more donors were more often from Caucasian origin, compared with Caucasian origin for patients with 30 donors. CONCLUSION: Adequate transfusion support could be guaranteed for most but not all refractory patients. More non-Caucasian donors are required to ensure the availability of HLA-matched donors for all patients in the Netherlands.

Investigation of the Relationship Between BK Virus and Human Leukocyte Antigens in Kidney Transplant Recipients.

OBJECTIVES: The main function of HLA is to present antigens to lymphocytes and to initiate specific immune responses. Autoimmune, viral, allergic, and neurologic diseases have been found to be related to HLA molecules. In renal transplant, the main target of the recipient's immune system is the HLA molecules on the surface of donor cells. HLA also plays a role in the development of an immune response to viral infections. After renal transplant, BK virus infections may occur due to immunosuppression. Here, we investigated the relationship between HLA and BK virus in renal transplant recipients. MATERIALS AND METHODS: This retrospective study investigated HLA-A, HLA-B, and HLA-DR tissue typing before renal transplant. DNA was isolated from whole blood, and tissue typing tests were performed based on polymerase chain reaction. Patients were tested for BK virus posttransplant using DNA isolated from urine and/or plasma samples. RESULTS: We found HLA-B*13 allele to be a protective factor (P < .049; odds ratio: 0.131; 95% confidence interval, 0.017-1.029) and HLA-DRB1*03 allele to be a possible risk factor (P < .029; odds ratio: 2.521; 95% confidence interval, 1.157-5.490) against BK virus. No significant relationships were found between BK virus and age, sex, donor type, and HLA mismatch. CONCLUSIONS: HLA class I molecules are known to be effective against viruses with the help of cytotoxic T cells. HLA-B*13 alleles within the HLA class I molecules were identified as protective factors against BK virus. HLA class II is associated with CD4-positive T cells that help secrete immune system cytokines, playing a role in stimulating and suppressing the immune system. We demonstrated that HLA-DRB1*03 allele could be a risk factor against BK virus. This allele may be associated with immunomodulatory cytokine secretion of the immune system.

The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) Score for HLA Class I Graft-versus-Host Disparity Is Associated with Increased Acute Graft-versus-Host Disease in Haploidentical Transplantation with Post-Transplantation Cyclophosphamide.

The Predicted Indirectly Recognizable HLA Epitopes (PIRCHE) score quantifies the number of PIRCHEs in patient-donor pairs and represents an in silico measure of indirect alloreactivity. This biologic process is defined as T cell recognition of epitopes derived from mismatched, allogeneic HLA peptides that are subsequently presented by shared HLA molecules. Its association with clinical outcome has not been examined in haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplantation cyclophosphamide (PTCy). We hypothesized that the PIRCHE score (PS) would correlate with indirect alloreactivity and predict graft-versus-host disease (GVHD) risk and the incidence of relapse after haplo-HCT with PTCy. We retrospectively analyzed 148 patients who underwent peripheral blood stem cell T cell-replete haplo-HCT with PTCy at a single center between 2009 and 2016. For each patient-donor pair, the PS was calculated using the PIRCHE online matching tool. PSs were categorized by class and vector. The median class I graft-versus-host (GVH) PS was 11 (range, 0 to 56), and the median class I host-versus-graft (HVG) PS was 10 (range, 0 to 51). Class I GVH PS was associated with increased risk of grade II-IV acute GVHD (adjusted hazard ratio, 1.03 per PS unit increase; 95% confidence interval, 1.01 to 1.05; P= .008) but not of chronic GVHD or relapse. Our data show that use of the PS is a novel strategy for predicting clinical outcome in haplo-HCT; further studies using registry data and prospective cohorts are warranted to validate these findings.