Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor David KavanaghORCiD, Rachel Challis



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


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.

Publication metadata

Author(s): Kavanagh D, McGlasson S, Jury A, Williams J, Scolding N, Bellamy C, Gunther C, Ritchie D, Gale DP, Kanwar YS, Challis R, Buist H, Overell J, Weller B, Flossmann O, Blunden M, Meyer EP, Krucker T, Evans SJ, Campbell IL, Jackson AP, Chandran S, Hunt DP

Publication type: Article

Publication status: Published

Journal: Blood

Year: 2016

Volume: 128

Issue: 24

Pages: 2824-2833

Print publication date: 15/12/2016

Online publication date: 15/12/2016

Acceptance date: 30/08/2016

Date deposited: 11/10/2016

ISSN (print): 0006-4971

ISSN (electronic): 1528-0020

Publisher: American Society of Hematology


DOI: 10.1182/blood-2016-05-715987

PubMed id: 27663672


Altmetrics provided by Altmetric


Funder referenceFunder name
Medical Research Council
Academy of Medical Sciences
512407National Health Medical Research Council
GU1212/1-2Deutsche Forschungsgemeinschaft
KFO 249/GU1212/1-1Deutsche Forschungsgemeinschaft
MH47680National Institutes of Health, National Institute of Mental Health
WT101153MAWellcome Trust