New Genetic Predictors for Abacavir Tolerance in HLA-B*57:01 Positive Individuals

2020 | Hum Immunol

Topic(s): Treatment as Prevention® |

Abstract:

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.

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Tel: 604-806-8477 | Fax: 604-806-9044
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(Please do not use any of these email addresses to send personal information or book an appointment. To book appointments or contact the H2H clinic, please call 604-416-1517 or fax: 604-564-4893. Do not send your or your client's personal information via email.)

© Copyright BC Centre for Excellence in HIV/AIDS
St. Paul's Hospital 608–1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6
Tel: 604-806-8477 | Fax: 604-806-9044
General inquiries: info@bccfe.ca
Media inquiries: communications@bccfe.ca
(Please do not use any of these email addresses to send personal information or book an appointment. To book appointments or contact the H2H clinic, please call 604-416-1517 or fax: 604-564-4893. Do not send your or your client's personal information via email.)

Our work serves clients and communities across British Columbia on lands and waters cared for and nurtured by the many distinct First Nations across the province. The BC-CfE humbly and gratefully acknowledge the stewards of these lands, particularly the xʷməθkʷəy̓əm (Musqueam), Sḵwx̱wú7mesh (Squamish), and səl̓ílwətaʔ (Tsleil-Waututh) on whose unceded, traditional and ancestral territories our offices are located.