Uncovering the role of interferons in immune-driven inflammatory disease

Written by:

Alessandro Sorrentino

Global Medical Head of Immunology

 


There are millions of patients around the world affected by immune-driven diseases, and AstraZeneca has a longstanding heritage following the science in immunology to uncover the underlying biology of an imbalanced immune system.1 Our scientific understanding of the immune system has led us to examine the impact of imbalances at the pathway level on a number of disease pathologies.2 We’re following the science to discover how we can intervene by regulating the activity within these key pathways, bringing back balance to the immune system with the aim of achieving disease control and ultimately clinical remission in targeted immune-driven diseases.

The type I interferon pathway plays a central role in immunity, enhancing the body’s ability to coordinate its immune response through complex interactions between components of the immune system – T-cells, B-cells and antibodies – that respond to internal and external threats. In a healthy immune system, type I interferons are essential for robust antiviral responses.3 But increased levels of type I interferons may trigger activation of the immune response against the body’s own tissue, which can lead to injury, inflammation, and permanent organ damage.4,5,6,7,8 This type I interferon dysfunction can be seen in a subpopulation of patients with inflammatory and immune-driven diseases.2

For instance, there is a growing body of evidence that the majority of adults with systemic lupus erythematosus have increased type I interferon signalling, which is known to be associated with disease activity and severity.8 Dysregulation of the type I interferon pathway can also be seen in Sjögren’s syndrome, myositis, and systemic sclerosis. Additionally, scientists have witnessed an interferon signature among a subset of patients with rheumatoid arthritis that suggests type I interferon plays a role for some patients with this disease.2,9 As part of our commitment to the millions of people living with a broad spectrum of immune-driven diseases, we are investigating the central role that type I interferons are thought to be playing in driving this wide range of immune-driven diseases.

In our efforts to map the therapeutic landscape of diseases that involve the type I interferon pathway, we bring together a wide range of medical experts — across fields as broad as rheumatology, oncology, infectious diseases and cardiology – in an annual scientific summit.2 Together, we explore these common pathways driving disease progression and discover new insights into the potential key drivers behind a range of diseases. Results of those discussions are then published to advance scientific exchange for the broader medical community.2

By targeting specific pathways within the body’s immune response, researchers can potentially develop tailored treatment options that advance personalised medicine and may help regulate the dysfunction within the immune system.2 Through our efforts, we hope to unlock opportunities leading to the development of new treatment approaches ultimately changing the natural course of these diseases.


References

1. Cooper GS, Bynum ML, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun. 2009;33(3-4):197-207. 

2. Crow MK, Rönnblom L. Report of the inaugural Interferon Research Summit: interferon in inflammatory diseases. Lupus Science & Medicine. 2018;5.

3. Murira A, Lamarre A. Type-I Interferon Responses: From Friend to Foe in the Battle against Chronic Viral Infection. Front. Immunol. 2016;10.

4. Crow MK. Type I Interferon in the Pathogenesis of Lupus. J Immunol. 2014;192(12):5459-5468.

5. Zharkova O, Celhar T, Cravens PD, et al. Pathways leading to an immunological disease: systemic lupus erythematosus. Rheumatology (Oxford). 2017;65(suppl_1):i55-i66.

6. Humbert M, Andersson TL, Buhl R. Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma. Allergy. 2008;63:1567-80.

7. Finn PW, Bigby TD. Innate immunity and asthma. Proc Am Thorac Soc. 2009;6(3):260-265.

8. Lauwerys BR, Ducreux J, Houssiau FA. Type I interferon blockade in systemic lupus erythematosus: where do we stand? Rheumatology. 2014;53:1369-1376.

9. Riggs JM, Hanna RN, Rajan B, et al. Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus. Lupus Science & Medicine 2018;5.


Veeva ID: Z4-28508

Date of preparation: November 2020


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