HLA Disease Association and Protection in HIV Infection among African Americans and Caucasians
30
Citation
0
Reference
10
Related Paper
Citation Trend
Abstract:
In a previous investigation, we demonstrated an increased progression of overt AIDS in the African American population compared to the Caucasian population as reflected by the significantly lower absolute number of CD4+ lymphocytes detected in the African American population in an earlier study. The present study elucidates some of the possible genetic factors which may contribute to disease association or protection against HIV infection. The HLA phenotypes expressed as A, B, C, DR and DQw antigens were revealed by the Amos-modified typing procedure. NIH scoring was utilized to designate positive cells taking up trypan blue. A test of proportion equivalent to the χ2 approximation was used to compare the disease population (n = 62; 38 African Americans, 24 Caucasians) to race-matched normal heterosexual local controls (323 African Americans, 412 Caucasians). Significant p values were corrected for the number of HLA antigens tested. HLA markers associated with possible protection from infection for African Americans were Cw4 and DRw6, whereas Caucasians expressed none. Disease association markers present in the African American population were A31, B35, Cw6, Cw7, DR5, DR6, DR11, DRwl2, DQw6 and DQw7, whereas in the Caucasian population A28, Aw66, Bw48, Bw65, Bw70, Cw7, Cw8, DRw10, DRw12, DQw6 and DQw7 were demonstrated. The highest phenotypic frequency for a disease association marker in the study was for HLA-DR5 (62.9%) in the HIV-infected African American population without Kaposi's sarcoma compared to a frequency of 28.9% for the regional control group (p = 0.0012). We conclude that genetic factors do have a role in HIV infection since only 50–60% of those exposed to the AIDS virus will become infected.Keywords:
Ancestry-informative marker
The human leukocyte antigen (HLA) system is a group of genes coding for proteins that are central to the adaptive immune system and identifying the specific HLA allele combination of a patient is relevant in organ donation, risk assessment of autoimmune and infectious diseases and cancer immunotherapy. However, due to the high genetic polymorphism in this region, HLA typing requires specialized methods. We investigated the performance of five next-generation-sequencing (NGS) based HLA typing tools with a non-restricted license namely HLA*LA, Optitype, HISAT-genotype, Kourami and STC-Seq. This evaluation was done for the five HLA loci, HLA-A, -B, -C, -DRB1 and -DQB1 using whole-exome sequencing (WES) samples from 829 individuals. The robustness of the tools to lower coverage was evaluated by subsampling and HLA typing 230 WES samples at coverages ranging from 1X to 100X. The typing accuracy was measured across four typing resolutions. Among these, we present two clinically-relevant typing resolutions, which specifically focus on the peptide binding region. On average, across the five HLA genes, HLA*LA was found to have the highest typing accuracy. For the individual genes, HLA-A, -B and -C, Optitype’s typing accuracy was highest and HLA*LA had the highest typing accuracy for HLA-DRB1 and -DQB1. The tools’ robustness to lower coverage data varied widely and further depended on the specific HLA locus. For all class I loci, Optitype had a typing accuracy above 95% (according to the modification of the amino acids in the functionally relevant portion of the protein) at 50X, but increasing the depth of coverage beyond even 100X could still improve the typing accuracy of HISAT-genotype, Kourami, and STC-seq across all five HLA genes as well as HLA*LA’s typing accuracy for HLA-DQB1. HLA typing is also used in studies of ancient DNA (aDNA), which often is based on lower quality sequencing data. Interestingly, we found that Optitype’s typing accuracy is not notably impaired by short read length or by DNA damage, which is typical of aDNA, as long as the depth of coverage is sufficiently high.
Cite
Citations (2)
Concordance
Cite
Citations (0)
HLA typing in solid organ transplantation (SOT) is necessary for determining HLA-matching status between donor-recipient pairs and assessing patients' anti-HLA antibody profiles. Histocompatibility has traditionally been evaluated based on serologically defined HLA antigens. The evolution of HLA typing and antibody identification technologies, however, has revealed many limitations with using serologic equivalents for assessing compatibility in SOT. The significant improvements to HLA typing introduced by next-generation sequencing (NGS) require an assessment of the impact of this technology on SOT. We have assessed the role of high-resolution 2-field HLA typing (HR-2F) in SOT by retrospectively evaluating NGS-typed pre- and post-SOT cases. HR-2F typing was highly instructive or necessary in 41% (156/385) of the cases. Several pre- and posttransplant scenarios were identified as being better served by HR-2F typing. Five different categories are presented with specific case examples. The experience of another center (Temple University Hospital) is also included, whereby 21% of the cases required HR-2F typing by Sanger sequencing, as supported by other legacy methods, to properly address posttransplant anti-HLA antibody issues.
Tissue typing
Histocompatibility
Histocompatibility Testing
Sanger sequencing
Cite
Citations (49)
The HLA complex is the most polymorphic genetic system in man yet known. The variability of the HLA antigens is given by the presence of many alleles of the HLA genes. Requirements for compatibility of HLA antigens in organ and bone marrow transplantations, and also in the determination of genetic risk factors in autoimmune diseases evoke strong pressure on progress in HLA typing methods, mainly for increasing their sensitivity and resolution. For typing of the HLA antigens there are used cellular, serological, biochemical and DNA methods. For HLA class I typing there following tests are used: cytotoxic test (serological), CML (cellular), 1D--IEF (biochemical), RFLP, SSO, SSP--PCR, and SBT (DNA methods). For HLA class II typing, cytotoxic test (cellular), MLC (serological), RFLP, SSO, SSP--PCR, and SBT (DNA methods) are used. DNA methods represent the modern trend in the area of HLA typing and it will probably replace larger part of other HLA typing techniques. In our article, we describe the principles of methods that are used for HLA typing.
Tissue typing
Histocompatibility Testing
HLA-B
Histocompatibility
Cite
Citations (1)
The human leukocyte antigen (HLA) system plays a critical role in the human immune system and is strongly associated with immune recognition and rejection in organ transplantation. HLA typing method has been extensively studied to increase the success rates of clinical organ transplantation. However, while polymerase chain reaction sequence-based typing (PCR-SBT) remains the gold standard, cis/trans ambiguity and nucleotide sequencing signal overlay during heterozygous typing present a problem. The high cost and low processing speed of Next Generation Sequencing (NGS) also render this approach inadequate for HLA typing.To address these limitations of the current HLA typing methods, we developed a novel typing technology based on nucleic acid mass spectrometry (MS) of HLA. Our method takes advantage of the high-resolution mass analysis function of MS and HLAMSTTs (HLA MS Typing Tags, some short fragment PCR amplification target products) with precise primer combinations.We correctly typed HLA by measuring the molecular weights of HLAMSTTs with single nucleotide polymorphisms (SNPs). In addition, we developed a supporting HLA MS typing software to design PCR primers, construct the MS database, and select the best-matching HLA typing results. With this new method, we typed 16 HLA-DQA1 samples, including 6 homozygotes and 10 heterozygotes. The MS typing results were validated by PCR-SBT.The MS HLA typing method is rapid, efficient, accurate, and readily applicable to typing of homozygous and heterozygous samples.
Cite
Citations (2)
Cite
Citations (0)
Human leukocyte antigen (HLA) typing is largely performed by use of PCR-based techniques in patients that require stem cell transplantation. In this chapter, HLA typing by sequencing-based typing techniques is described.
Tissue typing
Cite
Citations (10)
Human leukocyte antigen(HLA) is the key antigen mediating rejection and panel reactive antibody(PRA) represent anti-HLA antibodies in circulation.HLA typing and PRA testing are carried out generally before organ transplantation.With research on the relationship among HLA,PRA and heart transplantation developing,the value of HLA typing and PRA testing in heart transplantation has received more attention and their clinical using strategy has been improved.This article will review the strategy of HLA typing,the clinical value of HLA typing,time-selection in HLA typing,reason and mechanism of rising PRA,clinical sense of PRA testing and treatment of sensitized patients.
Panel reactive antibody
Tissue typing
Histocompatibility Testing
Cite
Citations (0)
Comprehensive and accurate human leukocyte antigen (HLA) typing within a short turnaround time is a crucial initial step for allocating deceased donor organs for transplantation. Erroneous HLA typing of deceased donors can be catastrophic and result in recipient death, failed transplant, and organ wastage due to inappropriately matched donors. The real-time polymerase chain reaction method is widely used as the sole method for HLA typing of deceased donors because of its simplified workflow. Herein, we have reported cases of four deceased donors showing discrepant HLA typing discovered using two independent methods concurrently. The HLA typing of these donors could have been erroneously reported if a single method had been used, which would have profound patient safety implications. In one case, the drop out of HLA-DR7 using a single method could have resulted in harmful organ allocation if the organ was transplanted after a virtual crossmatch to a sensitized candidate showing strong donor-specific HLA-DR7 antibodies. In conclusion, this case series suggests that concurrent dual typing is essential for accurate HLA typing of deceased donors. This strategy is vital because precise HLA typing is critical for accurate virtual crossmatching, which facilitates continuous distribution and broader geographic sharing of the deceased donor organ.
Tissue typing
Histocompatibility Testing
Cite
Citations (5)
This paper constitutes a feasibility report on the use of the human leukocyte antigen (HLA) system for the typing of dried bloodstains. Antigens tested include the HLA-A2, A3, A10, B7, B8, and B14 alleles. An aging study conducted on A3 positive bloodstains showed that HLA-A3 could be reliably detected on bloodstains stored up to 30 days at 22 degrees C. Unlike most earlier reports on HLA typing of bloodstains, no cross-reactivity problems were detected with the antisera used in this study. In addition to the successful typing of bloodstains, we were also able to type fresh, neat seminal and saliva stains in the A2 and A10 antigenic systems.
Histocompatibility Testing
Tissue typing
Cite
Citations (5)