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.
Prof Oliver Fitzgerald, St Vincent’s University Hospital