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

Pavlos, Rebecca; Deshpande, Pooja; Chopra, Abha; Leary, Shay; Strautins, Kaija; Nolan, David; Thorborn, Daren; Shaefer, Mark; Rauch, Andri; Dunn, David; Montaner, Julio; Rachlis, Anita; Almeida, Coral-Ann; Choo, Linda; James, Ian; Redwood, Alec J; Li, Yueran; Gaudieri, Silvana; Mallal, Simon A and Phillips, Elizabeth J (2020). New genetic predictors for abacavir tolerance in HLA-B*57:01 positive individuals. Human immunology, 81(6), pp. 300-304. Elsevier 10.1016/j.humimm.2020.02.011

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Infectiology

UniBE Contributor:

Rauch, Andri

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0198-8859

Publisher:

Elsevier

Language:

English

Submitter:

Annelies Luginbühl

Date Deposited:

20 Apr 2020 16:00

Last Modified:

03 Jun 2020 01:32

Publisher DOI:

10.1016/j.humimm.2020.02.011

PubMed ID:

32173028

Uncontrolled Keywords:

Abacavir hypersensitivity syndrome Endoplasmic reticulum aminopeptidase 1 Human leukocyte antigen

BORIS DOI:

10.7892/boris.142241

URI:

https://boris.unibe.ch/id/eprint/142241

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