New genetic predictors for abacavir tolerance in HLA-B*57:01 positive individuals.

Pavlos R, Deshpande P, Chopra A, Leary S, Strautins K, Nolan D, Thorborn D, Shaefer M, Rauch A, Dunn D, Montaner J, Rachlis A, Almeida CA, Choo L, James I, Redwood AJ, Li Y, Gaudieri S, Mallal SA, Phillips EJ
Hum Immunol. 2020 81 (6): 300-304

PMID: 32173028 · PMCID: PMC7266722 · DOI:10.1016/j.humimm.2020.02.011

Abacavir hypersensitivity syndrome (ABC HSS) is strongly associated with carriage of human leukocyte antigen (HLA)-B*57:01, which has a 100% negative predictive value for the development of ABC HSS. However, 45% of individuals who carry HLA-B*57:01 can tolerate ABC. We investigated immune and non-immune related genes in ABC HSS (n = 95) and ABC tolerant (n = 43) HLA-B*57:01 + patients to determine other factors required for the development of ABC HSS. Assignment of phenotype showed that ABC HSS subjects were significantly less likely than tolerants to carry only ERAP1 hypoactive trimming allotypes (p = 0.02). An altered self-peptide repertoire model by which abacavir activates T cells is in keeping with observation that endoplasmic reticulum aminopeptidase 1 (ERAP1) allotypes that favour efficient peptide trimming are more common in ABC HSS patients compared to patients who tolerate ABC. Independently, non-specific immune activation via soluble cluster of differentiation antigen 14 (sCD14) may also influence susceptibility to ABC HSS.

Copyright © 2020 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

MeSH Terms (19)

Allergens Aminopeptidases Anti-HIV Agents Dideoxynucleosides Drug-Related Side Effects and Adverse Reactions Drug Hypersensitivity Syndrome Female Genetic Association Studies Genetic Predisposition to Disease Genotype HIV-1 HIV Infections HLA-B Antigens Humans Lipopolysaccharide Receptors Male Minor Histocompatibility Antigens Phenotype Retrospective Studies

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