[Pubmed] Azathioprine therapy induces selective NK cell Depletion and IFN-γ Deficiency predisposing to herpes virus reac

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J Allergy Clin Immunol. 2022 Sep 16:S0091-6749(22)01187-3. doi: 10.1016/j.jaci.2022.09.010. Online ahead of print.

ABSTRACT

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 dissect specific effects of Azathioprine use on the systemic immune signature. Therapy-associated clinical features were analyzed in two independent cohorts of Myasthenia gravis patients.

RESULTS: Azathioprine therapy selectively induced pronounced CD56dimCD16+ NK cell depletion and concomitant IFN-γ deficiency. Cytokine profiling revealed a specific contraction of classical Th1 cells during Azathioprine treatment. We further observed an increased occurrence of re-activations of endogenous latent herpes viruses in the Azathioprine-treated group compared to Myasthenia gravis patients not receiving immunomodulatory treatment that was validated in an independent cohort.

CONCLUSION: Our study highlights the risk of developing adverse events during Azathioprine therapy and suggests that NK cell monitoring could be valuable in clinical practice.

PMID:36122787 | DOI:10.1016/j.jaci.2022.09.010


Source: https://pubmed.ncbi.nlm.nih.gov/3612278 ... 5&v=2.17.8