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Lupus

Autoimmune disease

At a glance

How is the molecule β2GPI involved in Antiphospholipid Syndrome?

Lead researcher

Dr Thomas McDonnell

Institution

University College London

Status

Awarded and preparing to start

Amount awarded

£260,486

Last updated

11/12/19

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Antiphospholipid Syndrome (APS) is an autoimmune disorder that affects approximately 0.3-1% of the population. It is closely associated with lupus and these two autoimmune conditions often occur in the same patient.

In a healthy immune system, proteins called antibodies attack and destroy disease-causing organisms such as bacteria. However, in autoimmune diseases the immune system malfunctions, resulting in antibodies attacking the body’s own healthy cells. These malfunctioning antibodies are called autoantibodies.

Dr McDonnell’s work focuses on a particular molecule that is targeted by the autoantibodies associated with APS: Beta-2-Glycoprotein I (β2GPI). The role of β2GPI in the body is yet to be fully determined, however this protein is one of very few known to interact with both the immune system and the coagulation system (a system composed of cells, proteins and processes that mediate blood clotting). Interestingly, β2GPI is the only protein known to both increase and decrease the function of the immune system and the activity of the coagulation system.

The coagulation system controls how the blood clots. This system is of particular importance for patients with APS as common symptoms of the disease include thrombosis (blood clots) and strokes (blood clot or blood vessel rupture in the brain).

Current treatment focuses on treating the symptoms of APS but not the underlying cause. Patients are given blood thinners (anticoagulants) to help alleviate the possibility of thrombosis and stroke.

Dr McDonnell aims to understand how β2GPI affects blood clotting and immune function. Specifically, Dr McDonnell will look at how the structure of β2GPI affects these functions, to improve our knowledge of the molecule’s involvement in APS.

β2GPI has two known structures: an O shape and a J shape. It is hypothesised that these two conformations have different effects on the coagulation and immune systems. Dr McDonnell will compare the differences in the structure of β2GPI in APS patients and healthy individuals. This may help to elucidate why some people develop APS and others don’t because the immune system may be stimulated more powerfully by specific β2GPI structures.

In addition, Dr McDonnell aims to manipulate the structure of β2GPI in the laboratory, to test how different shapes alter the effect on clotting, immune function and interaction with autoantibodies.

By increasing our understanding of disease mechanisms underpinning APS, Dr McDonnell’s work will drive this field of research forward and help to identify new targets for treatment, screening and diagnosis of APS.

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Autoimmune disease - Lupus

  • Why is there a need to fund new research?

    Lupus is a poorly understood autoimmune disease with limited treatment options.

    Despite several known triggers of lupus, the exact cause of the disease is unknown and there is currently no full cure.

    Living with lupus can be extremely challenging. 65 per cent of lupus sufferers report dealing with pain as the most difficult aspect of managing the disease. Early intervention can improve management of lupus, however the lack of understanding surrounding lupus contributes to delays in diagnosis. Current research estimates it takes over six years to be correctly diagnosed.

    There is a high clinical need to better our understanding of the disease and improve treatment options and outcomes for patients.

    The Foundation is delighted to have committed over £1 million to lupus research and contribute to changing the lives of those with lupus.

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