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A transgenic mouse model for HLA-B*57:01-linked abacavir drug tolerance and reactivity.

Author: AkueAdovi D, AnanthulaSuryatheja, BoydLisa F, CardoneMarco, GarciaKarla, GebreyohannesSintayehu, JuengstLeslie, MarguliesDavid H, MattsonElliot, NatarajanKannan, NorcrossMichael A, PuigMontserrat, RoderiquezGregory, TilahunMulualem E, YanoMasahide

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.

Overview

This study aimed to study HLA-linked adverse drug reactions (ADRs) to the HIV reverse transcriptase inhibitor abacavir (ABC) in vivo. The researchers generated HLA-B*57:01-Tg mice, which demonstrated ABC tolerance in vivo despite in vitro activation of CD8+ T cells. The study revealed that ABC induced CD8+ T cells with an anergy-like phenotype in immunocompetent Tg animals, preventing ADRs. However, depletion of CD4+ T cells prior to ABC administration led to the induction of systemic ABC-reactive CD8+ T cells with an effector-like and skin-homing phenotype, resulting in CD8+ infiltration and inflammation in drug-sensitized skin. The study emphasizes the importance of both HLA genetic risk and immunoregulatory host factors in determining the outcome of ABC administration.
Paper Details　
Original Abstract of the Article :
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, s...See full text at original site
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引用元：
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025983/

データ提供：米国国立医学図書館（NLM）

A Transgenic Mouse Model for HLA-B*57:01-Linked Abacavir Drug Tolerance and Reactivity

The field of drug development is a complex and challenging journey, much like navigating a vast and treacherous desert. This research delves into the intricate world of adverse drug reactions, specifically focusing on abacavir hypersensitivity, a life-threatening condition associated with the HLA-B*57:01 allele. The study explores how HLA-B*57:01-linked abacavir hypersensitivity can be studied in a new transgenic mouse model. This model, like a trusty camel navigating a treacherous landscape, can be used to understand the mechanisms underlying this hypersensitivity reaction, helping us to develop safer and more effective medications for patients.

HLA-B*57:01 Plays a Key Role in Abacavir Hypersensitivity

The study reveals that HLA-B*57:01 is a key player in abacavir hypersensitivity. It’s like a hidden spring in the desert—a seemingly insignificant factor that can have a profound impact on the surrounding landscape. This research provides valuable insights into the interplay between genetic predisposition and immune responses, which can help us to better understand and prevent adverse drug reactions.

Building a Safer Future for Drug Development

The transgenic mouse model developed in this study offers a powerful tool for understanding and mitigating drug hypersensitivity. This research, like a trailblazing caravan, paves the way for a safer and more personalized approach to drug development, ensuring that patients receive the treatment they need without the risk of life-threatening adverse reactions. By understanding the intricacies of drug-immune interactions, we can create a more secure and predictable journey through the desert of drug development.

Dr. Camel's Conclusion

This study provides a roadmap for navigating the complex landscape of drug hypersensitivity, offering a better understanding of the interplay between genetics and immune responses. The transgenic mouse model is a valuable tool for researchers to explore the mechanisms underlying abacavir hypersensitivity, paving the way for safer and more targeted treatments. We must continue our exploration of the desert of drug development to ensure that our journeys are safe, effective, and ultimately beneficial for all.

Date :
  1. Date Completed 2019-09-16
  2. Date Revised 2019-09-16
Further Info :

Pubmed ID

29782330

DOI: Digital Object Identifier

PMC6025983

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Article Analysis
・Side Effects of abacavir
SNS
PICO Info
in preparation
Languages

English

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