绿帽换妻

What we do

Autoimmune connective tissue diseases are an overlapping set of systemic diseases that cause inflammation in multiple organs. We are a group of investigators with diverse interests in these conditions that range from basic laboratory science through to clinical trials and outcome measures research.

The ANA-associated diseases include systemic lupus erythematosus, Sjogren’s Syndrome, inflammatory myopathies, mixed and undifferentiated connective tissue diseases and research is led by Ed Vital, Miriam Wittmann and Paul Emery. The research programme in scleroderma and related diseases is led by Francesco Del Galdo, Maya Buch and Paul Emery). These diseases may affect many organs of the obody including the skin, joints, kidneys, lungs and brain. They are uncommon but unmet needs for treatment are severe with marked morbidity and mortality despite best therapy. More than 2000 patients with these conditions have been enrolled into local registries and observational studies with rich clinical phenotyping and sample collections. ANCA vasculitis is another multisystem autoimmune disease with therapeutic and mechanistic similarities.

Polymyalgia Rheumatica and Large vessel vasculitis are related diseases that occur predominantly in older people. This programme is led by Sarah Mackie. The predominant therapy for these diseases is glucocorticoids, which have significant toxicity. The use, minimisation and toxicity of glucocorticoids is a related theme of this research programme.

Research themes

These diverse areas of research are linked by several cross-cutting themes. Further details on individual projects can be found below.

Pre-clinical and early disease

The mainstay of treatment for autoimmune connective tissue diseases is immunosuppression but this seldom leads to cure and may cause long term toxicity. The initiation of diseases like SLE and scleroderma are now recognised to occur in a stepwise manner over many years. A key focus of research is in the prediction of disease in individuals “at risk” so that disease can be predicted, diagnosed before clinical features begin, and to allow future disease prevention trials.

Skin Disease

Diseases like discoid lupus, SLE and scleroderma all have prominent involvement of the skin. Linked to the dermatorheumatology theme in LIRMM, we have substantial research programmes investigating basic and translational immunology in the skin, mechanisms of scarring and novel non-invasive biomarkers and novel locally directed therapeutics.

Imaging

Novel imaging tools are a strength of research in LIRMM. Musculoskeletal imaging with ultrasound and MRI, such as in the phenotyping of lupus arthritis, linked to the LIRMM imaging group. In scleroderma, tools such as optical coherence tomography, capillaroscopy and laser Doppler imaging allow insights in early stages of disease, clinical outcomes and mechanism.

B cell therapies and biomarkers

B cell targeted therapies, such as rituximab, belimumab and humanised anti-CD20 molecules, are used across the spectrum of ANA- and ANCA-associated disease. LIRMM has the largest single-centre cohort of rituximab-treated patients in the world across all indications. We pioneered the use of flow cytometry to understand responses and develop novel therapeutic strategies in clinical trials.

Type I interferons and other biomarkers

Type I interferons play a crucial role in the pathogenesis of a range of autoimmune diseases. We have developed novel biomarkers to characterise interferon status in blood and tissue and shown how these can be used for prediction of disease and other clinical outcomes. These projects are linked to translational immunology studying the regulation of interferon production in blood and tissue. Our large cohorts and sample collections are ideal for the study of other biomarkers. For example, novel serum fibrosis biomarkers to predict outcomes in scleroderma.

Collaborative and student opportunities

Work with industry includes investigator-initiated clinical trials of novel therapies and strategies, early phase and proof of concept studies. Through our clinical cohorts and translational immunology we are ideally place to work in biomarker development and validation. We have developed both imaging and clinical endpoints for use in clinical trials as well as stratifying populations to determine optimal target populations for interventions in trials and routine clinical practice.

Postgraduate student opportunities include lab based and clinical research fellow projects. Previous PhD and MSc students have been successful in obtaining fellowships from the NIHR, industry, charities, 绿帽换妻 Teaching Hospitals and the 绿帽换妻.

Collaborative research projects include MRC stratified medicine consortia and multicentre academic and industry-sponsored clinical trials.

Funding

Key publications

 

Who we are

People

View our team members