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Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature

Gale, DP; Kavanagh, D; McGlasson, S; Jury, A; Williams, J; Scolding, N; Bellamy, C; ... Hunt, DPJ; + view all (2016) Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature. Blood , 128 (24) pp. 2824-2833. 10.1182/blood-2016-05-715987. Green open access

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Abstract

Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular TMA has been reported in association with recombinant type I interferon therapies, with recent concern regarding the use of interferon in multiple sclerosis patients. However a causal association has yet to be demonstrated. Here we adopt a combined clinical and experimental approach to provide evidence of a such an association between type I interferon and TMA. We show the clinical phenotype of cases referred to a national centre is uniformly consistent with a direct dose-dependent drug-induced TMA. We then show that dose-dependent microvascular disease is seen in a transgenic mouse model of interferon toxicity. This includes specific microvascular pathological changes seen in patient biopsies, and is dependent on transcriptional activation of the interferon response through the type I interferon receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I interferon and thrombotic microangiopathy. As such, recombinant type I interferon therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation.

Type: Article
Title: Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/blood-2016-05-715987
Publisher version: https://doi.org/10.1182/blood-2016-05-715987
Language: English
Additional information: This research was originally published in Blood. Gale, DP; Kavanagh, D; McGlasson, S; Jury, A; Williams, J; Scolding, N; Bellamy, C. Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature. Blood; 128 (24): pp. 2824-2833. © the American Society of Hematology.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1515825
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