Psoriasis

Background

Psoriasis is a common skin disease that causes huge distress for patients and for which treatment remains elusive. The condition appears as unsightly patches (plaques) that can itch, form painful splits in the skin and can cause painful joints. One of the main problems for psoriasis sufferers lies in the way it looks and the social implications of the skin disease that severely affect the quality of life of the sufferer.

At present, there is no cure for psoriasis but there are effective cream and lotion treatments to control the symptoms of mild psoriasis. A patient with extensive psoriasis will need to attend a dermatology outpatient unit or be admitted to a dermatology ward for 3-4 weeks for treatment. Even following effective treatment, there is a tendency for the symptoms of psoriasis to return.

Current Research

Novel Therapeutics for Psoriasis

Research Focus

Our work is evaluating the pathophysiology and progression of psoriasis in patients and animal models. In conjunction with leading industry partners, we are developing and testing novel therapeutic compounds to alleviate the symptoms associate with the psoriasis. 

Lead Investigator

Prof Martin Steinhoff, UCD Charles Institute of Dermatology

Researcher

Dr Alan Corcoran, Postdoctoral Research Fellow

Inflammatory Diseases Pathogenesis

Research Focus

Chronic or inappropriate inflammatory responses contribute to the pathogenesis of several diseases including psoriasis and arthritis. Important scientific advances indicate that the progression of these diseases may result from a switch in the type of cells present at sites of inflammation that ultimately leads to damage and destruction of the affected tissue.

A major focus of this research programme is to understand the events and mechanisms involved in switching cells during the inflammatory response. A thorough understanding of these processes may assist in the diagnosis of inflammatory disease and facilitate the introduction of effective treatments in the early stages of disease. The study of inflamed tissue and derived cells represents a central feature of this research programme, which will provide information with important clinical significance. Furthermore, these studies may potentially open new avenues for the treatment of chronic inflammatory disease.

Lead Investigator

Dr Evelyn Murphy, UCD Conway Institute of Biomolecular & Biomedical Research

Immune Function in Psoriasis

Research Focus

The Health Research Board awarded a funding grant of €285,000 to Prof Brian Kirby, principal investigator of the dermatology research group in the Education & Research Centre, St Vincent’s University Hospital. The grant runs for three years from September 2012 and will examine the function of Langerhans cells and other dendritic cells in psoriasis. The group hopes that this research will help to define the immune mechanisms that contribute to the pathogenesis of this chronic immune mediated skin disease.

Lead Investigator

Prof Brian Kirby, St Vincent’s University Hospital

Genetics of Psoriasis and Psoriatic Arthritis

Research Focus

Psoriatic arthritis (PsA) is a chronic, inflammatory disease of synovial joints, enthesis and spine. It is found in up to 30% of patients with psoriasis and leads to joint damage in about 50% of cases within 2 years of diagnosis [Kane et al. 2001].

Professor Oliver FitzGerald leads both clinical and biomedical (PsA) research nationally and internationally in an effort to understand the pathogenesis of the disease, improve early diagnosis, accurately chart disease progress and response to treatment and identify new therapeutic targets.

Together with Prof Brian Kirby (SVUH)Prof Alan Irvine (SJH)Dr Ross McManus (TCD) and Dr David Kane (AMNCH), he established a genetic repository in psoriasis and psoriatic arthritis that now comprises DNA samples from more than 1000 patients. Almost 450 type 1 psoriasis patient samples were contributed to the Wellcome Trust psoriasis genome-wide association study in a collaborative effort to expand scientific knowledge on the genetics of psoriasis and psoriatic arthritis.

Identification of novel susceptibility loci Working with Prof Robert Winchester at Columbia University, New York, Prof FitzGerald and his team have recently found that HLA-B27 is a marker for musculoskeletal involvement in PsA [Winchester et al. 2012].

As well as conducting his own research in this area, Prof FitzGerald contributes to the genome wide screening initiative, Psoriatic Arthritis Genetics in Europe (PAGE) consortium. Perhaps the most important finding from this initiative is that of a new association of TRAF3IP2 gene in psoriatic arthritis [Huffmeier et al. 2010]. TRAF3IP2 codes for an adaptor protein known as ACT-1, which is a key component of the inflammatory response (IL-17) pathway.

FitzGerald’s group have recently suggested that key mutation in Act1 could lead to a greater association of the IL-17 receptor with TRAF2/TRAF5 which in turn suggests an alternative function for IL-17 in PsA [Doyle et al. 2012]. The correlation of ΔCD3 with ΔDAS28 and ΔMRI following biologic treatment in this cohort identifies ΔCD3 as a candidate biomarker of disease response.

Together these results suggest that changes in T cell (CD3) synovial infiltration, and not macrophage infiltration as in rheumatoid arthritis, may be used as an early marker of treatment response in PsA.

Identification of novel biomarkers of treatment response and of change in bone density In order to seek a potential biomarker of treatment response in psoriatic arthritis (PsA), FitzGerald’s group are investigating whether changes in immunohistochemical markers of synovial inflammation correlate with changes in DAS28 (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in 27 patients with PsA treated with a biologic agent.

EU FP7 “MIAMI” programme grant: Biomarkers and diagnostics for chronic inflammatory diseases of the joints and/or digestive system This funding will provide support for using proteomic approaches to developing biomarkers of severity and of treatment response. Together with Professor Stephen Pennington in UCD Conway Institute, the group have recently described a panel of proteins that predict treatment response to anti-TNF therapies in PsA [Collins et al 2012].

For the first time, these studies offer the possibility that response to treatment may be predicted by a panel of proteins, thus raising the exciting idea that decisions to prescribe may be more scientifically-based.

Lead Investigator

Prof Oliver Fitzgerald, St Vincent’s University Hospital

Immune Function in Psoriasis

Established in 2005, the Psoriatic Arthritis Genetics in Europe (PAGE) consortium aims to undertake studies to investigate the genetic basis of psoriatic arthritis primarily in terms of susceptibility but also outcome, where data allows, in a European population.

A large cohort of over 2000 patients has been collected and a number of publications have already resulted from the work of this consortium including the publication of the first genome-wide association study (GWAS) in PsA.

Prof Oliver Fitzgerald, St Vincent's University Hospital is a member of PAGE.