Kavanagh, D;
McGlasson, S;
Jury, A;
Williams, J;
Scolding, N;
Bellamy, C;
Gunther, 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.
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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 (IFN) therapies, with recent concern regarding the use of IFN 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 such an association between type IIFN and TMA. We show that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA. We then show that dosedependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon a/b receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. As such, recombinant type I IFN 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: | http://doi.org/10.1182/blood-2016-05-715987 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL 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 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/1539135 |
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