» Articles » PMID: 36248878

HLA Allele-specific Expression: Methods, Disease Associations, and Relevance in Hematopoietic Stem Cell Transplantation

Overview
Journal Front Immunol
Date 2022 Oct 17
PMID 36248878
Authors
Affiliations
Soon will be listed here.
Abstract

Varying HLA allele-specific expression levels are associated with human diseases, such as graft versus host disease (GvHD) in hematopoietic stem cell transplantation (HSCT), cytotoxic T cell response and viral load in HIV infection, and the risk of Crohn's disease. Only recently, RNA-based next generation sequencing (NGS) methodologies with accompanying bioinformatics tools have emerged to quantify HLA allele-specific expression replacing the quantitative PCR (qPCR) -based methods. These novel NGS approaches enable the systematic analysis of the HLA allele-specific expression changes between individuals and between normal and disease phenotypes. Additionally, analyzing HLA allele-specific expression and allele-specific expression loss provide important information for predicting efficacies of novel immune cell therapies. Here, we review available RNA sequencing-based approaches and computational tools for NGS to quantify HLA allele-specific expression. Moreover, we explore recent studies reporting disease associations with differential HLA expression. Finally, we discuss the role of allele-specific expression in HSCT and how considering the expression quantification in recipient-donor matching could improve the outcome of HSCT.

Citing Articles

Variation within the non-coding genome influences genetic and epigenetic regulation of the human leukocyte antigen genes.

Arumugam T, Adimulam T, Gokul A, Ramsuran V Front Immunol. 2024; 15:1422834.

PMID: 39355248 PMC: 11442197. DOI: 10.3389/fimmu.2024.1422834.


Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Tong K, Meng Y, Zhang L, Lei X, Liu Q, Guan X Ann Hematol. 2024; 103(7):2485-2497.

PMID: 38709259 DOI: 10.1007/s00277-024-05787-9.


Narrative Review Explaining the Role of , , and Molecules in COVID-19 Disease in and around Africa.

Naidoo L, Arumugam T, Ramsuran V Infect Dis Rep. 2024; 16(2):380-406.

PMID: 38667755 PMC: 11049896. DOI: 10.3390/idr16020029.


Nucleotide alterations in the HLA-C class I gene can cause aberrant splicing and marked changes in RNA levels in a polymorphic context-dependent manner.

Mizutani A, Suzuki S, Shigenari A, Sato T, Tanaka M, Kulski J Front Immunol. 2024; 14:1332636.

PMID: 38327766 PMC: 10847315. DOI: 10.3389/fimmu.2023.1332636.


Comparison between qPCR and RNA-seq reveals challenges of quantifying HLA expression.

Aguiar V, Castelli E, Single R, Bashirova A, Ramsuran V, Kulkarni S Immunogenetics. 2023; 75(3):249-262.

PMID: 36707444 PMC: 9883133. DOI: 10.1007/s00251-023-01296-7.

References
1.
Ramsuran V, Naranbhai V, Horowitz A, Qi Y, Martin M, Yuki Y . Elevated expression impairs HIV control through inhibition of NKG2A-expressing cells. Science. 2018; 359(6371):86-90. PMC: 5933048. DOI: 10.1126/science.aam8825. View

2.
Dellgren C, Nehlin J, Barington T . Cell surface expression level variation between two common Human Leukocyte Antigen alleles, HLA-A2 and HLA-B8, is dependent on the structure of the C terminal part of the alpha 2 and the alpha 3 domains. PLoS One. 2015; 10(8):e0135385. PMC: 4530957. DOI: 10.1371/journal.pone.0135385. View

3.
Hiraki A, Fujii N, Murakami T, Kiura K, Aoe K, Yamane H . High frequency of allele-specific down-regulation of HLA class I expression in lung cancer cell lines. Anticancer Res. 2004; 24(3a):1525-8. View

4.
Bray N, Pimentel H, Melsted P, Pachter L . Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol. 2016; 34(5):525-7. DOI: 10.1038/nbt.3519. View

5.
Weider T, Richardson S, Morgan N, Paulsen T, Dahl-Jorgensen K, Hammerstad S . HLA Class I Upregulation and Antiviral Immune Responses in Graves Disease. J Clin Endocrinol Metab. 2020; 106(4):e1763-e1774. PMC: 7993595. DOI: 10.1210/clinem/dgaa958. View