The HLA system: immunobiology, HLA typing, antibody screening and crossmatching techniques

2010 ◽  
Vol 63 (5) ◽  
pp. 387-390 ◽  
Author(s):  
W M Howell ◽  
V Carter ◽  
B Clark
Keyword(s):  
Critical Role ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Antibody Screening ◽  
Leukocyte Antigen ◽  
Hla System ◽  
Clinical Transplantation ◽  
Cross Matching ◽  
Immunological Barrier ◽  
Introductory Review

The Human Leukocyte Antigen (HLA) system plays a critical role in regulating the immune response. As a consequence of its role in immune regulation and exquisite polymorphism, the HLA system also constitutes an immunological barrier which must be avoided or otherwise overcome in clinical transplantation. This introductory review provides a brief summary of the immunobiology of the HLA system and methodology for HLA typing, antibody screening and patient-donor cross-matching. This constitutes a basis for consideration of the importance of these procedures in the system-specific reviews which follow.

scholarly journals arcasHLA: high resolution HLA typing from RNA seq

2018 ◽  
Author(s):  
Rose Orenbuch ◽  
Ioan Filip ◽  
Devon Comito ◽  
Jeffrey Shaman ◽  
Itsik Pe'er ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Mhc Class Ii ◽  
Critical Role ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Sequencing Data ◽  
Leukocyte Antigen ◽  
Hla Genes ◽  
Biological Dataset ◽  
High Level

Human leukocyte antigen (HLA) locus makes up the major compatibility complex (MHC) and plays a critical role in host response to disease, including cancers and autoimmune disorders. In the clinical setting, HLA typing is necessary for determining tissue compatibility. Recent improvements in the quality and accessibility of next-generation sequencing have made HLA typing from standard short-read data practical. However, this task remains challenging given the high level of polymorphism and homology between the HLA genes. HLA typing from RNA sequencing is further complicated by post-transcriptional splicing and bias due to amplification. Here, we present arcasHLA: a fast and accurate in silico tool that infers HLA genotypes from RNA sequencing data. Our tool outperforms established tools on the gold-standard benchmark dataset for HLA typing in terms of both accuracy and speed, with an accuracy rate of 100% at two field precision for MHC class I genes, and over 99.7% for MHC class II. Importantly, arcasHLA takes as its input pre-aligned BAM files, and outputs three-field resolution for all HLA genes in less than 2 minutes. Finally, we discuss evaluate the performance of our tool on a new biological dataset of 447 single-end total RNA samples from nasopharyngeal swabs, and establish the applicability of arcasHLA in metatranscriptome studies. arcasHLA is available at https://github.com/RabadanLab/arcasHLA.

scholarly journals arcasHLA: high-resolution HLA typing from RNAseq

2019 ◽  
Vol 36 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Rose Orenbuch ◽  
Ioan Filip ◽  
Devon Comito ◽  
Jeffrey Shaman ◽  
Itsik Pe’er ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Critical Role ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Supplementary Information ◽  
Sequencing Data ◽  
Leukocyte Antigen ◽  
Biological Dataset ◽  
Hla Genotypes ◽  
High Level

Abstract Motivation The human leukocyte antigen (HLA) locus plays a critical role in tissue compatibility and regulates the host response to many diseases, including cancers and autoimmune di3orders. Recent improvements in the quality and accessibility of next-generation sequencing have made HLA typing from standard short-read data practical. However, this task remains challenging given the high level of polymorphism and homology between HLA genes. HLA typing from RNA sequencing is further complicated by post-transcriptional modifications and bias due to amplification. Results Here, we present arcasHLA: a fast and accurate in silico tool that infers HLA genotypes from RNA-sequencing data. Our tool outperforms established tools on the gold-standard benchmark dataset for HLA typing in terms of both accuracy and speed, with an accuracy rate of 100% at two-field resolution for Class I genes, and over 99.7% for Class II. Furthermore, we evaluate the performance of our tool on a new biological dataset of 447 single-end total RNA samples from nasopharyngeal swabs, and establish the applicability of arcasHLA in metatranscriptome studies. Availability and implementation arcasHLA is available at https://github.com/RabadanLab/arcasHLA. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Human Leukocyte Antigen and Red Blood Cells Impact Umbilical Cord Blood CD34+ Cell Viability after Thawing

2019 ◽  
Vol 20 (19) ◽  
pp. 4875 ◽  
Author(s):  
Vanegas ◽  
Galindo ◽  
Páez-Gutiérrez ◽  
González-Acero ◽  
Medina-Valderrama ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Cell Viability ◽  
Cord Blood ◽  
Red Blood Cells ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Blood Cells ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Leukocyte Antigen

Hematopoietic progenitor cell (HPC) transplantation is a treatment option for malignant and nonmalignant diseases. Umbilical cord blood (UCB) is an important HPC source, mainly for pediatric patients. It has been demonstrated that human leukocyte antigen (HLA) matching and cell dose are the most important features impacting clinical outcomes. However, UCB matching is performed using low resolution HLA typing and it has been demonstrated that the unnoticed mismatches negatively impact the transplant. Since we found differences in CD34+ viability after thawing of UCB units matched for two different patients (p = 0.05), we presumed a possible association between CD34+ cell viability and HLA. We performed a multivariate linear model (n = 67), comprising pre-cryopreservation variables and high resolution HLA genotypes separately. We found that pre-cryopreservation red blood cells (RBC), granulocytes, and viable CD34+ cell count significantly impacted CD34+ viability after thawing, along with HLA-B or -C (R2 = 0.95, p = 0.01; R2 = 0.56, p = 0.007, respectively). Although HLA-B*40:02 may have a negative impact on CD34+ cell viability, RBC depletion significantly improves it.

scholarly journals Genetic diversity among volunteer donors of bone marrow in southeastern Brazil, according to the HLA system

2014 ◽  
Vol 132 (3) ◽  
pp. 158-162
Author(s):  
Letícia Sarni Roque ◽  
Rodolpho Telarolli-Junior ◽  
Leonor Castro Monteiro Loffredo
Keyword(s):  
Bone Marrow ◽  
Human Leukocyte ◽  
Mixed Race ◽  
University Hospital ◽  
Southeastern Brazil ◽  
Leukocyte Antigen ◽  
Hla System ◽  
History Of ◽  
Allelic Group ◽  
Southeastern Region

CONTEXT AND OBJECTIVE: Checking the histocompatibility of the molecules of the human leukocyte antigen (HLA) system is vital for performing bone marrow transplantation with allogeneic material. The objective of this study was to characterize bone marrow donors according to gender, age, ethnicity and HLA groups at a regional hemotherapy center in Brazil.DESIGN AND SETTING:Descriptive study on registered donors at a regional hemotherapy center in a public university hospital in the southeastern region of Brazil.METHODS: The records of 66,780 donors who were registered between 2005 and June 2011 were consulted, and the variables studied were tabulated.RESULTS:There were equal numbers of male and female donors and 82.8% of them were under 45 years of age. In terms of ethnicity, 77.3% declared themselves to be white, 15.0% mixed race, 5.7% black and 2% others. In terms of immunogenetic characterization, the most frequent HLA-A allelic group was HLA-A*02, with 39.20% of the donors; in the HLA-B allelic group, the most common was HLA-B*35, with 14.18%; while in the HLA-DRB1 allelic group, the most frequent was HLA-DRB1*03, with 17.03%. Comparison between these results and data from the Brazilian Bone Marrow Donor Registry (REDOME) showed that there were demographic and immunogenetic differences due to the history of immigration in the region of Ribeirão Preto, in southeastern Brazil.CONCLUSIONS: The results reinforce the importance of understanding the demographic and immunogenic profile of regions of Brazil, in order to reduce the waiting time for a histocompatible donor.

scholarly journals Performance Characteristics of Updated INNO-LiPA Assays for Molecular Typing of Human Leukocyte Antigen A (HLA-A), HLA-B, and HLA-DQB1 Alleles

2004 ◽  
Vol 11 (2) ◽  
pp. 430-432 ◽  
Author(s):  
Karen De Vreese ◽  
Rachel Barylski ◽  
Fiona Pughe ◽  
Miriam Bläser ◽  
Colin Evans ◽  
...  
Keyword(s):  
Performance Evaluation ◽  
Human Leukocyte Antigen ◽  
Molecular Typing ◽  
Human Leukocyte ◽  
Performance Characteristics ◽  
Hla Typing ◽  
Tissue Typing ◽  
Leukocyte Antigen ◽  
Antigen A ◽  
Accuracy Rates

ABSTRACT We carried out a multicenter performance evaluation of three new DNA-based human leukocyte antigen (HLA) typing assays: INNO-LiPA HLA-A Update, INNO-LiPA HLA-B Update, and INNO-LiPA HLA-DQB1 Update. After optimization, the accuracy rates were all 100%, and the final observed resolutions were 99.4, 92.4, and 85.6%, respectively. These rapid and easy-to-perform assays yielded results fully concordant with other DNA-based tissue typing tests.

scholarly journals HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection

2021 ◽  
Author(s):  
Danillo G Augusto ◽  
Tasneem Yusufali ◽  
Noah D Peyser ◽  
Xochitl Butcher ◽  
Gregory M Marcus ◽  
...  
Keyword(s):  
Critical Role ◽  
Human Leukocyte ◽  
Asymptomatic Infection ◽  
Baseline Survey ◽  
Symptomatic Infection ◽  
Symptomatic Disease ◽  
Leukocyte Antigen ◽  
Hla Genotyping ◽  
Asymptomatic Individuals ◽  
Test Result

Background. Evidence has shown that a large proportion of SARS-CoV-2 infected individuals do not experience symptomatic disease. Owing to its critical role in immune response, we hypothesized that variation in the human leukocyte antigen (HLA) loci may underly asymptomatic infection. Methods. We enrolled 29,947 individuals registered in the National Marrow Donor Program for whom high-resolution HLA genotyping data were available in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Among 21,893 individuals who completed the baseline survey, our discovery (N=640) and replication (N=788) cohorts were comprised of self-identified White subjects who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci (HLA-A, -B, -C, -DRB1, -DQB1) with asymptomatic vs. symptomatic infection. Results. HLA-B*15:01 was significantly increased in asymptomatic individuals in the discovery cohort compared to symptomatic (OR = 2.45; 95%CI 1.38-4.24, p = 0.0016, pcorr = 0.048), and we reproduced this association in the replication cohort (OR= 2.32; 95%CI = 1.10-4.43, p = 0.017). We found robust association of HLA-B*15:01 in the combined dataset (OR=2.40 95% CI = 1.54-3.64; p = 5.67 x10-5) and observed that homozygosity of this allele increases more than eight times the chance of remaining asymptomatic after SARS-CoV-2 infection (OR = 8.58, 95%CI = 1.74-34.43, p = 0.003). Finally, we demonstrated the association of HLA-B*15:01 with asymptomatic SARS-Cov-2 infection is enhanced by the presence of HLA-DRB1*04:01 Conclusion. HLA-B*15:01 is strongly associated with asymptomatic infection with SARS-CoV-2 and is likely to be involved in the mechanism underlying early viral clearance.

scholarly journals Familial Pemphigus Vulgaris Occured in a Father and Son as the First Confirmed Cases

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Ali Haydar Eskiocak ◽  
Birgul Ozkesici ◽  
Soner Uzun
Keyword(s):  
Genetic Predisposition ◽  
Human Leukocyte ◽  
Pemphigus Vulgaris ◽  
Hla Typing ◽  
Enzyme Linked Immunosorbent Assay ◽  
Leukocyte Antigen ◽  
Hla Genes ◽  
Mother And Daughter ◽  
First Occurrence ◽  
Father And Son

Pemphigus vulgaris (PV) is a chronic autoimmune bullous disease of the skin and mucous membranes. Although there is some evidence pointing towards a genetic predisposition by some human leukocyte antigen (HLA) genes, familial occurrence of PV is very rare. Most of the familial PV cases so far reported have been in mother and daughter and in siblings. PV in father and son, as presented here, has not been reported in the literature before, except an unconfirmed report. The diagnosis of PV was established by histologic, cytologic studies and enzyme linked immunosorbent assay (ELISA) in Case1and by ELISA and BIOCHIP indirect immunofluorescence test in Case2. The son was responsive to moderate doses of methylprednisolone, with the treatment continuing with tapered doses. The father was in a subclinic condition; consequently, only close follow-up was recommended. HLA typing studies revealed identical HLA alleles of HLA-DR4 (DRB1⁎04) and HLA-DQB1⁎03in both of our cases; this had been found to be associated with PV in prior studies. Familial occurrences of PV and related HLA genes indicate the importance of genetic predisposition. The first occurrence of confirmed familial PV in father and son is reported here.

scholarly journals PIRCHE-II: an algorithm to predict indirectly recognizable HLA epitopes in solid organ transplantation

2019 ◽  
Vol 72 (1-2) ◽  
pp. 119-129 ◽  
Author(s):  
Kirsten Geneugelijk ◽  
Eric Spierings
Keyword(s):  
Human Leukocyte Antigen ◽  
Organ Transplantation ◽  
Graft Survival ◽  
Solid Organ Transplantation ◽  
Human Leukocyte ◽  
Solid Organ ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
Hla System ◽  
Hla Mismatches

AbstractHuman leukocyte antigen (HLA) mismatches between donors and recipients may lead to alloreactivity after solid organ transplantation. Over the last few decades, our knowledge of the complexity of the HLA system has dramatically increased, as numerous new HLA alleles have been identified. As a result, the likelihood of alloreactive responses towards HLA mismatches after solid organ transplantation cannot easily be assessed. Algorithms are promising solutions to estimate the risk for alloreactivity after solid organ transplantation. In this review, we show that the recently developed PIRCHE-II (Predicted Indirectly ReCognizable HLA Epitopes) algorithm can be used to minimize alloreactivity towards HLA mismatches. Together with the use of other algorithms and simulation approaches, the PIRCHE-II algorithm aims for a better estimated alloreactive risk for individual patients and eventually an improved graft survival after solid organ transplantation.

scholarly journals Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability

Blood ◽  
2010 ◽  
Vol 115 (18) ◽  
pp. 3671-3677 ◽  
Author(s):  
Barbara Sarina ◽  
Luca Castagna ◽  
Lucia Farina ◽  
Francesca Patriarca ◽  
Fabio Benedetti ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Hodgkin Lymphoma ◽  
Autologous Transplantation ◽  
Multivariable Analysis ◽  
Human Leukocyte ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Hla Typing ◽  
Human Leukocyte Antigen Typing ◽  
Leukocyte Antigen

Abstract Hodgkin lymphoma relapsing after autologous transplantation (autoSCT) has a dismal outcome. Allogeneic transplantation (alloSCT) using reduced intensity conditioning (RIC) is a salvage option, but its effectiveness is still unclear. To evaluate the role of RIC alloSCT, we designed a retrospective study based on the commitment of attending physicians to perform a salvage alloSCT; thus, only Hodgkin lymphoma patients having human leukocyte antigen-typing immediately after the failed autoSCT were included. Of 185 patients, 122 found an identical sibling (55%), a matched unrelated (32%) or a haploidentical sibling (13%) donor; 63 patients did not find any donor. Clinical features of both groups did not differ. Two-year progression-free (PFS) and overall survival (OS) were better in the donor group (39.3% vs 14.2%, and 66% vs 42%, respectively, P < .001) with a median follow-up of 48 months. In multivariable analysis, having a donor was significant for better PFS and OS (P < .001). Patients allografted in complete remission showed a better PFS and OS. This is the largest study comparing RIC alloSCT versus conventional treatment after a failed autoSCT, indicating a survival benefit for patients having a donor.

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