Researching into sticky blood

Dr Maria Laura Bertolaccini 

Was appointed as the first Louise Gergel Fellow in November 2005

Extracts of her work and research papers are shown below

August 2013 Report

by Dr Laura Bertolacinni, Louise Gergel Fellow

Highlights

Research at the Graham Hughes Lupus Research Laboratory, Lupus Research Unit is based around a translational program with the aim of understanding the mechanisms of immunologically mediated thrombosis and vascular damage in lupus and antiphospholipid syndrome.  Other lines of research focus on prognostic markers for nephritis and neuropsychiatric lupus.

Our line of research includes:

New specificities for the antiphospholipid syndrome

2) Seronegative Antiphospholipid Syndrome project

3) Clinical accuracy of antiphospholipid antibody testing

4) Assessing the risk of developing the clinical manifestations of APS

5) Characterisation of the role of monocytes in the APS


Research

by Dr Laura Bertolacinni, Louise Gergel Fellow

The antiphospholipid syndrome (APS) is a disease also called 'sticky blood' syndrome in which the blood has a tendency to clot spontaneously. This clotting disorder can affect any vessel in the body or even, during pregnancy can be a major cause of miscarriages and fetal death. The majority of people with APS are aged between 20 and 50 years, although all age groups can be affected. It seems to be more frequent in women than men because of its effect on pregnancy.

There are two main blood tests that are used for diagnosis: 1) the anticardiolipin test (aCL) and 2) the lupus anticoagulant test (LA). Although these tests are the most clinically useful, there are a small number of people with APS (about 20%) in whom one or other test will be negative.

International research efforts are directed in 3 broad based aspects – the basic mechanisms of the disease (why patients develop the condition in the first place and why some patients develop thrombosis and others not), the clinical ramifications of the disease (a condition which can potentially affect any organ must impinge on all branches on medicine) and methods to improve and ‘fine tune’ treatment.

The common thread linking patients with APS is the presence of antibodies. Antibodies would normally have the task of defending against foreign invaders such as viruses or bacteria but in this disease, antibodies known as “antiphospholipid antibodies” (aPL) react to self-molecules, particularly phospholipid-protein complexes. The association between aPL and thrombosis is strong, but the exact mechanism for the thrombosis remains uncertain. aPL have been shown to alter platelets, clotting proteins and the blood vessel lining itself (endothelium).

One attractive theory is that these antibodies affect the clotting proteins of the blood. Recently, we have identified new targets for the aPL, which are being extensively investigated in our laboratory. Antibodies to prothrombin (a coagulation protein) have been shown to be specific markers for thrombosis. Most significantly, we have also shown that some patients with APS related clinical features, which are negative for aCL and LA had antiprothrombin antibodies, suggesting that testing for these antibodies could be of added clinical benefit. Antibodies to Factor XII, another protein involved in the clotting process, have also been found in patients with APS and their immunological characteristics are being investigated.

Further reading

1.         Bertolaccini ML, Hughes GR. Antiphospholipid antibody testing: which are most useful for diagnosis? Rheum Dis Clin North Am 2006; 32: 455-63

2.         Bertolaccini ML, Khamashta MA. Laboratory diagnosis and management challenges in the antiphospholipid syndrome. Lupus 2006; 15: 172-8

        Khamashta MA. Hughes syndrome. Antiphospholipid syndrome. Khamashta MA, ed. London: Springer-Verlag, 2006

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Dr Vera Ripoll

New Louise Gergel Fellow - September 2017

My career started out in Colombia working at the Institute of Immunology, a centre with a well-recognised reputation for studies in tropical diseases, focusing on Malaria, which is the leading cause of mortality in Colombia. Through this period I developed a passion to further my career in immunology and moved to Australia to undertake a PhD.

Recognising that macrophages are one of the leading contributors to immune related diseases my PhD focused on identifying novel macrophage-specific transcripts to contribute to the understanding of macrophage function with a view to generating candidate therapeutic targets in the treatment of immune related diseases. During this period my research was part of a major translational research project involving a joint venture between AstraZeneca and three Australian universities. In what was a successful period of research I was able to publish high impact factor papers through collaborations and partnerships with the Australian immunology community.

To expand on my international experience I undertook a post-doc position at the MRC Mammalian Genetics Unit. The Oxfordshire based unit is at the international forefront in the use of ENU (n-ethyl-n-nitrosurea) mutagenesis, a powerful methodology used to study the relationship between genes and diseases in mouse models. During this time I led several successful projects to expand our library of immune-related alleles and generate new models for inflammatory diseases.

Having established prolonged success using mouse models to explore immunological based disease mechanisms I was motivated to undertake translational research and joined UCL to broaden my research experience in a clinical setting. I have spent the last 6 years working on the pathogenesis of APS, with access to a unique cohort of patients. The project successfully identified a number of novel targets involved in the diverse pathogenic mechanisms of the disease. This success culminated in a publication in a highly recognised journal for blood-related diseases (Blood).

With this fellowship I propose to build on the exciting results generated from my research at UCL, I am particularly interested in pursuing a new biological target in the treatment of APS. This new target is in a process called autophagy, which allow cells to degrade unwanted material or to recycle nutrients. I believe that a malfunction in autophagy leads the immune system to attack the body itself, causing symptoms of disease. I have already obtained promising results indicating that APS-derived antibodies act to reduce autophagy. I now need to understand where exactly in the process these antibodies are acting and to use a number of drugs, including those commercially available, to determine which would be best for reversing the effects of APS antibodies on autophagy and treating the disease.

Outside of work I like to spend time with my family, in particular my 3 year-old son Felipe. I enjoy reading good Spanish novels, admiring impressionism and post- impressionism paintings and foreign movies, which I often use to keep up my French. Finally, I love traveling to different beaches around the world to make up for the typical British weather when I’m at home.

"I am particularly interested in pursuing a new biological target in the treatment of APS.

This new target is in a process called autophagy, which allow cells to degrade unwanted material or to recycle nutrients.

I believe that a malfunction in autophagy leads the immune system to attack the body itself, causing symptoms of disease.

I have already obtained promising results indicating that APS-derived antibodies act to reduce autophagy.

I now need to understand where exactly in the process these antibodies are acting and to use a number of drugs, including those commercially available, to determine which would be best for reversing the effects of APS antibodies on autophagy and treating the disease."