scholarly journals Human Leukocyte Antigen-C and Haplotypes: Associations with Resistance and Susceptibility to HIV-1 Infection among Serodiscordant Couples in Nigeria

2021 ◽  
Author(s):  
Ngozi Mirabel Otuonye ◽  
Ma Luo ◽  
Onaiwu Idahosa Enabulele ◽  
Ayorinde James ◽  
Felix Emele ◽  
...  
Keyword(s):  
High Resolution ◽  
Human Leukocyte ◽  
Hiv Positive ◽  
Serodiscordant Couples ◽  
Leukocyte Antigen ◽  
Class 1 ◽  
Allele Specific ◽  
Hla Class 1 ◽  
Susceptibility And Resistance ◽  
Hiv 1

ABSTRACTINTRODUCTIONThe Human Leucocyte Antigen (HLA) class-1 is known to play a significant role in mediating resistance or susceptibility to HIV infection in the clinical course of AIDS. Recent studies have identified HLA-C as a key molecule that affects HIV disease progression. However, the role of HLA class 1 in heterosexual HIV-1 susceptibility or resistance in serodiscordant couples is not known in Nigeria. Therefore, this study evaluated the association between HLA-C susceptibility and resistance in HIV-1 transmission amongst heterosexual serodiscordant couples in Nigeria.METHODSA total of 271 serodiscordant, concordant HIV positive and negative couples who gave informed consent were enrolled into this study. Extracted genomic DNA was sequenced for high resolution HLA-C class 1 genotypes using allele-specific primers (on exons 2 and 3) for HLA-C sequencing and typing.RESULTSThe highest frequency distribution of high-resolution HLA-C alleles observed in the HIV positive subjects were: HLA-C*040101 178 (35.0%) followed by C*0701 124 (24.9%) compared with HIV negative subjects: C*040101 108(39.0%) followed by C*0701 64(24.7%). Alleles C*070201 (OR = 4.19, P<0.05) and C*0804 (OR = 3, P<0.045) were found to be independently associated with HIV-1 susceptibility in the cohort of serodiscordant couples. HLA-C*0802 (OR=0.5. P<0.005) and C*0304 (OR=0.34. P<0.002) were significantly associated with HIV-1 resistance to HIV-1 infection among the cohort.CONCLUSIONThe result has contributed to the importance of how host HLA-C genetic factors can influence HIV-1 disease susceptibility (HLA-C*070201; C*0804) and resistance (HLA-C*0802; C*0304) in serodiscordant couples. This information may contribute to the development of future effective HIV vaccine in Nigeria.

Post-Transfusion Purpura Mimicking Idiopathic Thrombocytopenic Purpura: A Case Report

2019 ◽  
Vol 50 (4) ◽  
pp. 396-400
Author(s):  
Chelsea Milito ◽  
Debra Masel ◽  
Kelly Henrichs ◽  
Amy E Schmidt ◽  
Scott Kirkley ◽  
...  
Keyword(s):  
Idiopathic Thrombocytopenic Purpura ◽  
Human Leukocyte ◽  
Caucasian Woman ◽  
Severe Thrombocytopenia ◽  
Cell Transplant ◽  
Screening Assay ◽  
Thrombocytopenic Purpura ◽  
Leukocyte Antigen ◽  
Class 1 ◽  
Hla Class 1

AbstractThe main clinical distinction between post-transfusion purpura (PTP) and idiopathic thrombocytopenic purpura (ITP) is the sudden development of severe thrombocytopenia in the days after transfusion. Herein, we report the case of a 53-year-old Caucasian woman who developed multiple myeloma (MM) after peripheral blood-stem-cell transplant (PBSCT), along with severe thrombocytopenia (with a nadir of 1 × 109/L); she also experienced severe adverse events after each platelet transfusion, including the first one. These reactions were absent with any other transfused blood products. The results of an human leukocyte antigen (HLA) class-1 panel reactive antibody assay were 0%, and the results of a platelet-antibody screening assay were positive for HLA class-1 antibodies and glycoprotein (Gp)IIb/IIIa antibodies. Her platelet count reached 42 × 109 per L on day 50, after rituximab on day 22 and daratumumab on day 29. Her clinical scenario was most consistent with the course of PTP.

scholarly journals Predicting toxicity and response to pembrolizumab through germline genomic HLA class 1 analysis

2020 ◽  
Author(s):  
Marco A J Iafolla ◽  
Cindy Yang ◽  
Vinod Chandran ◽  
Melania Pintilie ◽  
Quan Li ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Statistical Significance ◽  
Single Agent ◽  
Human Leukocyte ◽  
Immune Checkpoint Blockade ◽  
Peripheral Blood Mononuclear ◽  
Leukocyte Antigen ◽  
Whole Exome ◽  
Class 1 ◽  
Hla Class 1

Abstract Background Human leukocyte antigen class 1 (HLA-1)-dependent immune activity is linked to autoimmune diseases. HLA-1-dependent CD8+ T cells are required for immune checkpoint blockade (ICB) anti-tumor activity. It is unknown if HLA-1 genotype is predictive of toxicity to ICB. Methods Patients with advanced solid tumors stratified into five cohorts received single agent pembrolizumab (anti-PD-1) 200 mg IV every 3 weeks in an investigator-initiated phase II trial (INSPIRE study, NCT02644369). Germline whole exome sequencing (WES) of peripheral blood mononuclear cells was performed using the Illumina HiSeq2500 platform. HLA-1 haplotypes were predicted from WES using HLAminer and HLAVBSeq. Heterozygosity of HLA-A, -B and -C, individual HLA-1 alleles and HLA haplotype dimorphism at positions -21 M and -21 T of the HLA-A and -B leader sequence were analyzed as predictors of: toxicity defined as ≥ Grade 2 immune-related adverse events; and clinical benefit (CB) defined as complete or partial response, or stable disease for ≥ 6 cycles of pembrolizumab. Statistical significance tests were two-sided. Results In the overall cohort of 101 patients, the frequency of toxicity and CB from pembrolizumab was 22.8% and 25.7%, respectively. There was no association between any of the HLA-1 loci or alleles with toxicity. HLA-C heterozygosity had an association with decreased CB relative to HLA-C homozygosity when controlling for cohort (OR = 0.28, 95% CI 0.09–0.91, p = .04). HLA-A and -B haplotype -21 M/T dimorphism and heterozygosity of HLA-A, -B and -C were not predictive of outcomes. Conclusions HLA-C heterozygosity may predict decreased response to pembrolizumab. Prospective validation is required.

scholarly journals Influence of infused cell dose and HLA match on engraftment after double-unit cord blood allografts

Blood ◽  
2011 ◽  
Vol 117 (12) ◽  
pp. 3277-3285 ◽  
Author(s):  
Sharon Avery ◽  
Weiji Shi ◽  
Marissa Lubin ◽  
Anne Marie Gonzales ◽  
Glenn Heller ◽  
...  
Keyword(s):  
High Resolution ◽  
Cord Blood ◽  
Human Leukocyte ◽  
Transplant Recipients ◽  
Myeloablative Conditioning ◽  
Leukocyte Antigen ◽  
Cell Dose ◽  
Unit Unit ◽  
The Impact ◽  
Insight Into

Abstract The influence of cell dose and human leukocyte antigen (HLA) match on double-unit cord blood (CB) engraftment is not established. Therefore, we analyzed the impact of cell dose and high-resolution HLA match on neutrophil engraftment in 84 double-unit CB transplant recipients. The 94% sustained engraftment rate was accounted for by 1 unit in nearly all patients. Higher CD3+ cell doses (P = .04) and percentage of CD34+ cell viability (P = .008) were associated with unit dominance. After myeloablative conditioning, higher dominant unit total nucleated cell (TNC), CD34+ cell, and colony-forming unit doses were associated with higher sustained engraftment and faster neutrophil recovery (P = .07, P = .0008, and P < .0001, respectively). Total infused TNC (P = .0007) and CD3+ cell doses (P = .001) also significantly influenced engraftment. At high-resolution extensive donor-recipient HLA disparity was frequent, but had no influence on engraftment (P = .66), or unit dominance (P = .13). Although the unit-unit HLA match also did not affect sustained engraftment (P = 1.0), recipients of units closely (7-10 to 10-10) HLA-matched to each other were more likely to demonstrate initial engraftment of both units (P < .0001). Our findings have important implications for unit selection and provide further insight into double-unit biology.

Characteristics allelic of Human Leukocyte Antigen class I genotype and association with viral load and CD4 cell count in HIV-1 infected patients, Hanoi 2014 – 2016

2021 ◽  
Vol 31 (4) ◽  
pp. 43-50
Author(s):  
Tran Thi Minh Tam ◽  
Nguyen Thuy Linh ◽  
Phan Ha My ◽  
Nguyen Thi Lan Anh
Keyword(s):  
Viral Load ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Cd4 Cell Count ◽  
Leukocyte Antigen ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Hiv 1

Human Leukocyte Antigen (HLA) class I plays a regulatory role in cellular immune response to HIV-1 infection. The role of HLA alleles in HIV progression via viral load and CD4 cell count is well known. HLA class I is polymorphic and distributed differently by nation. This descriptive cross-sectional study was performed on 303 HIV-1 infected patients in 2014 - 2016, with aims to (i) characterize HLA class I genotype with 4-digit nomenclature and (ii) identify specifc alleles in correlate with CD4 cell counts and HIV viral load. 117 allele genotypes have been identifed, including 28 HLA-A alleles, 54 HLA-B alleles and 35 HLA-C alleles. The results showed that the most prevalent alleles in the population include A*11:01 (30.7%), B*15:02 (15.2%) and C*08:01 (17.1%). The frequency of haplotype created from these alleles is 8.4%. A*02:03, B*46:01 related to gender and ethnicity respectively. In conclusion, the study provided detailed pattern of HLA class I expression in a study population of HIV-1 infected patients and reported for the frst time the associated B*51:01, C*14:02 alleles associated to an increase in CD4 cell counts.

scholarly journals Human Leukocyte Antigen B58 Supertype and Human Immunodeficiency Virus Type 1 Infection in Native Africans

2006 ◽  
Vol 80 (12) ◽  
pp. 6056-6060 ◽  
Author(s):  
Aleksandr Lazaryan ◽  
Elena Lobashevsky ◽  
Joseph Mulenga ◽  
Etienne Karita ◽  
Susan Allen ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Leukocyte Antigen ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human Leukocyte ◽  
Subtype C ◽  
Leukocyte Antigen ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human leukocyte antigen (HLA) class I alleles can be grouped into supertypes according to their shared peptide binding properties. We examined alleles of the HLA-B58 supertype (B58s) in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-seropositive Africans (423 Zambians and 202 Rwandans). HLA-B and HLA-C alleles were resolved to four digits by a combination of molecular methods, and their respective associations with outcomes of HIV-1 infection were analyzed by statistical procedures appropriate for continuous or categorical data. The effects of the individual alleles on natural HIV-1 infection were heterogeneous. In HIV-1 subtype C-infected Zambians, the mean viral load (VL) was lower among B*5703 (P = 0.01) or B*5703-Cw*18 (P < 0.001) haplotype carriers and higher among B*5802 (P = 0.02) or B*5802-Cw*0602 (P = 0.03) carriers. The B*5801-Cw*03 haplotype showed an association with low VL (P = 0.05), whereas B*5801 as a whole did not. Rwandans with HIV-1 subtype A infection showed associations of B*5703 and B*5802 with slow (P = 0.06) and rapid (P = 0.003) disease progression, respectively. In neither population were B*1516-B*1517 alleles associated with more favorable responses. Overall, B58s alleles, individually or as part of an HLA-B-HLA-C haplotype, appeared to have a distinctive impact on HIV-1 infection among native Africans. As presently defined, B58s alleles cannot be considered uniformly protective against HIV/AIDS in every population.

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