Research programme to develop immunological biomarkers for chronic inflammatory diseases

Persistent inflammation and the activation of the immune system is the key pathological mechanism affecting many long-term conditions, such as rheumatoid arthritis, psoriasis, ulcerative colitis, and Crohn's disease and is the predominant mechanism underlying organ transplant rejection. But the molecular and cellular processes triggering these inflammatory and immune responses remain little understood.

A group of London-based researchers hope that by extending understanding of the biological processes, they will be able to identify 'biomarkers' in the tissue and blood, which in future could be used to diagnose these conditions, to predict how they will develop and how an individual will respond to treatment.

The -500,000 research programme is being carried out at National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, working in partnership with King's College Hospital NHS Foundation Trust and Barts and The London School of Medicine and Dentistry

Professor Frank Nestle, Mary Dunhill Chair of Cutaneous Medicine and Immunotherapy at King's College London, explains: "We want to test the theory that there are common immunological pathways underlying many chronic inflammatory diseases and that these could serve as valuable biomarkers for diagnostic, prognostic and therapeutic purposes."

Key to the success of this research programme is the Biomedical Research Centre's immune monitoring core, which consists of cutting-edge high throughput flow cytometric analysis and flow sorting equipment as well as multiplex cytokine analysis equipment. This technology enables researchers to analyse events within particular cell types involved in the body's immune response, such as T cells and dendritic cells, in minute detail with statistical accuracy.

In addition, the Centre's strategic agreement with BD Biosciences, a segment of BD, a leading global medical technology company, enables its investigators to access BD Biosciences' novel flow based technologies, reagents in the development pipeline and to co-develop and commercialise potential immunological biomarkers.

Researchers will use these technologies to study the activities within the cells of healthy volunteers to establish a range of variance in the normal population and develop a potential immunological signature (a combination of immune markers characteristic for a given cell type or its state of activation).

They will then test this signature using tissue and blood samples taken from patients with psoriasis, kidney transplant rejection and rheumatoid arthritis in the first instance to see if it can be accurately used for the early diagnosis of these conditions. Following this, they will undertake a series of prospective studies to test the predictive accuracy of the signatures in relation to disease progression and response to therapies, before studying other conditions, such as ulcerative colitis, Crohn's disease and transplant rejection.

Professor Graham Lord, Deputy Director of the Biomedical Research Centre said: "This research programme is hugely exciting as it brings our patients together with cutting-edge technology, basic science and clinical medicine. By carrying out detailed studies of cell activity, we aim to develop an immunological biomarker set that will transform the way that a number of specific inflammatory conditions are diagnosed and managed in future. Our patients will be the first to benefit from any new discoveries."

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