St Thomas' Lupus Unit: Our Research



by Dr Graham RV Hughes MD FRCP

Consultant Rheumatologist, St Thomas' Hospital, London

(First printed in Lupus UK News & Views, Spring 2000 Number 60)


Our Main research is summarised below:

1. GENETICS

It is widely believed that lupus is a genetically determined disease. Our huge lupus clinic (2,500 patients) allows us to carefully define "subsets" of patients and we are studying the genetic aspects of many of our patients with workers at Guys, in Stockholm, in Milan and in Sheffield.

2. HUGHES' SYNDROME

In 1983 we discovered a link between blood clotting ("sticky blood") and certain antibodies in lupus. These antibodies, called antiphospholipid antibodies, are seen in other, non-lupus diseases where excessive blood clotting is a problem. We are very intensely involved in the study of these patients (800 on our register)and the work in our laboratory concentrates on the mechanisms whereby the antibodies male the blood too "sticky". We are looking at the genetic, immunological and clinical features of the Syndrome.

3. THE BRAIN

Involvement of the brain in severe lupus has always been of central interest in our research unit, from the early 1970s, when we reported antibodies thought to cross-react with brain tissue, through the early 1980s when we reported the strong association of antiphospholipid antibodies and strokes. This was followed by studies of migraines, epilepsy, chorea (St Vitus Dance)in lupus and Hughes' Syndrome. In January 2000, we have a major study coming out in "Medicine" (Baltimore) which shows that some patients labelled as "multiple sclerosis" may, in fact, be wrongly diagnosed and have the much more treatable Hughes Syndrome (see Research Papers and Articles). Over the years we have shown that brain involvement in lupus, possibly the most frightening aspect of this disease, is usually very treatable.

4. THE HEART

A rare problem, seen in the occasional offspring of mothers with a certain antibody (anti-Ro)is heart block - a slow pulse rate which occurs in the developing foetus in-utero. Dr Patrick Gordon, a clinical research fellow in our unit, has been awarded a grant by the National heart Foundation to study this phenomenon - a study we are carrying out in collaboration with our department of Cardiology.

5. ARTERY DISEASE

One of the areas of most intense study is the finding that some patients with lupus and Hughes' Syndrome develop "early" artery disease, including strokes and heart attacks. In our unit, work led by Drs Munther Khamashta, Maria Cuadrado and Laura Bertolaccini is focusing on why some of the antibodies found in Hughes' Syndrome and lupus cross-react with "low density lipoproteins" - important molecules in the development of atheroma. Such is the importance of this work that in March 2000 a full issue of the journal LUPUS is being devoted to international studies on the subject.

6. KIDNEYS

Our combined renal unit (run in collaboration with Dr Ian Abbs) has a number of studies in progress, including the role of artery disease in lupus kidneys, studies of newer immunosuppressive agents in the management of the disease and newer, more precise scanning methods of testing kidney function.

7. LUNGS

Our unit (Dr Beverley Hunt) is coordinating a European wide study (Led by Dr Marie-Claire Boffa in Paris) of the rare condition "pulmonary hypertension" - raised blood pressure in the lung circulation. One of the benefits of such international collaboration is that rare, small-print yet very important conditions can be more meaningfully studied.

8. TREATMENT

We are actively involved in looking at different, and sometimes new, treatment options. Our unit led the way with a more conservative approach to treatment, notably with lower steroid doses (Clinic in Rheumatic Diseases: August 1979). We were involved in the first study of plasma exchange 25 years ago with Dr John Verrier-Jones (and are still involved in this work), in the widespread testing of antimalarial combinations, in low-dose pulse cyclophosphamide regimes (the St Thomas' Hospital regime), and more recently the use of Thalidomide in severe skin lupus. Other, as yet experimental, treatments have included Danazol, intravenous immunoglobulin (used mainly for patients with low platelet counts)and newer immunosuppressives. On a more routine basis, we are collaborating with colleagues on cholesterol management and the prevention and treatment of osteoporosis in steroid-treated patients.

9. OTHER CLINICAL STUDIES

Collaborated studies with other colleagues at St Thomas' and elsewhere include the role of photosensitivity on the skin is different lupus groups, studies of the role of the hormone prolactin in lupus, studies of low dose anticoagulant regimes in Hughes' Syndrome and aspects of pregnancy management in lupus.

10. INTERNATIONAL COLLABORATION

Our unit currently has 12 international research fellow from Japan, Spain, France, Italy, Argentina, the United States, Mexico and Brazil.

It is little surprise, therefore, that international collaborative studies are central to our research programme. We are part of the European-wide "Europlus" project - a computerised database linkup. We first started and have taken an active part in the international standardisation of tests for the antiphospholipid (Hughes') syndrome, unexciting but vital work.

Nearer to home, in collaboration with the Department of General Practice and Primary Care, King's College, London, we are studying the prevalence of lupus in the community. One of the curious discrepancies about lupus is the apparently high frequency in West Indians, but lower prevalence in West Africans. By coincidence, on our own doorstep is one of the few places in the world where West Indians and west Africans live together in a similar environment. We may be in an unique position to see whether this widely-quoted discrepancy is true or not.

Conclusions

I have listed some of the main research projects but, obviously, not by any means all. For those wishing to delve deeper there is our own L U P U S website http://www.lupus-support.org.uk, the Hughes' Syndrome website and the website of LUPUS: An International Journal.

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