Azathioprine therapy induces selective NK cell depletion and IFN-γ deficiency predisposing to herpesvirus reactivation.
Azathioprine
IFN-γ
NK cells
adverse effects
full-spectrum cytometry
herpesvirus
immune signature
immunosuppression
mass cytometry
myasthenia gravis
side effects
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
01 2023
01 2023
Historique:
received:
04
04
2022
revised:
17
08
2022
accepted:
01
09
2022
pubmed:
20
9
2022
medline:
11
1
2023
entrez:
19
9
2022
Statut:
ppublish
Résumé
Azathioprine is a widely prescribed drug for patients with chronic inflammatory diseases such as myasthenia gravis or organ transplant recipients. Azathioprine exerts immunosuppressive effects by inhibiting intracellular purine synthesis and reducing the numbers of circulating B and T lymphocytes. Case reports indicate increased risk for serious infections that can occur despite regular measurements of lymphocyte counts during azathioprine therapy. We sought to comprehensively investigate therapy-associated patient risks and the underlying immune dysfunction of azathioprine use. Peripheral blood leukocytes were analyzed using single-cell mass and spectral flow cytometry to detect specific effects of azathioprine use on the systemic immune signature. Therapy-associated clinical features were analyzed in 2 independent cohorts of myasthenia gravis patients. Azathioprine therapy selectively induced pronounced CD56 Our study highlights the risk of development of adverse events during azathioprine therapy and suggests that natural killer cell monitoring could be valuable in clinical practice.
Sections du résumé
BACKGROUND
Azathioprine is a widely prescribed drug for patients with chronic inflammatory diseases such as myasthenia gravis or organ transplant recipients. Azathioprine exerts immunosuppressive effects by inhibiting intracellular purine synthesis and reducing the numbers of circulating B and T lymphocytes. Case reports indicate increased risk for serious infections that can occur despite regular measurements of lymphocyte counts during azathioprine therapy.
OBJECTIVE
We sought to comprehensively investigate therapy-associated patient risks and the underlying immune dysfunction of azathioprine use.
METHODS
Peripheral blood leukocytes were analyzed using single-cell mass and spectral flow cytometry to detect specific effects of azathioprine use on the systemic immune signature. Therapy-associated clinical features were analyzed in 2 independent cohorts of myasthenia gravis patients.
RESULTS
Azathioprine therapy selectively induced pronounced CD56
CONCLUSION
Our study highlights the risk of development of adverse events during azathioprine therapy and suggests that natural killer cell monitoring could be valuable in clinical practice.
Identifiants
pubmed: 36122787
pii: S0091-6749(22)01187-3
doi: 10.1016/j.jaci.2022.09.010
pii:
doi:
Substances chimiques
Azathioprine
MRK240IY2L
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
280-286.e2Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.