ANNUAL REVIEW master Final3a - St Vincent's University Hospital

St. Vincent’s Healthcare Group Limited - Annual Review 2007
Education & Research
psoriatic arthritis (PsA) synovial tissue correlates with change in DAS28 following initiation of biologic
therapy. Finally Eliza is examining the role of TLRs in patients with PsA. Eliza has demonstrated expression
of TLR-2/4 in the endothelial and lining layer regions of the synovium. Currently she is stimulating primary
fibroblasts from patients with PsA with TLR-2 and 4 +/- cJun inhibitors and assessing regulation of
chemokines.
(3) Psoriasis/Psoriatic Arthritis
(i) Biomarkers of Biologic Treatment Response: As part of investigator-originated lead by Prof
FitzGerald, single-arm protocols looking at mechanisms of effect of biologic therapies, 6mm skin
biopsy (uninvolved at baseline only; leading edge of Ps lesion at baseline and follow-up) and synovial
membrane (obtained under local-anaesthetic at mini-arthroscopy pre-and post-biologic therapy)
samples are available for study following infliximab (n=15), IL-1Ra (n=12) and etanercept (n=15,).
Comparisons of immunohistochemical (IH) changes will be made with standard clinical measures and
with MRI changes in the affected knee joint. The IH and semi-quantitative MRI (collaboration with Dr.
Robin Gibney) analysis has now been completed and comparisons are being made with clinical
response markers. In addition, with Prof Patrick Brennan’s group from Imaging UCD, a more
quantitative measure of synovitis is being developed. Finally, funded by Abbott, a new post doctoral
scientist has been appointed who will be analysing differential protein expression in these patientderived
samples together with Prof Steve Pennington from UCD.
(ii) Expression and Regulation of Transcription factors in Ps/PsA: This work is lead by Dr. Evelyn
Murphy and Dr. Brian Kirby, the expression and regulation of NURR proteins pre-and post-treatment is
being explored. Findings have established the aberrant expression and distribution of the orphan
nuclear receptor NURR1 in psoriasis and suggest that clinical benefits of TNF-α inhibition may be
mediated through altered NURR1 activity. In addition, a recent paper suggests a key regulatory role for
the AP-1 transcription complex in Ps/PsA.
(iii) T cell Receptor Phenotype: Following on previous publications in PsA, the observations are
currently being extended, in collaboration with Prof Bob Winchester, to ankylosing spondylitis where the
patients are carefully HLA-matched. Preliminary results indicate significant clonal expansion within both
the CD4 and CD8 populations.
(iv) Synovial Proteomics Dr Emily Collins is examining proteomic profiles in PsA patients pre/post
biologic therapy. We are aiming to identify molecular biomarkers which predict response to anti-TNF·
therapy which are present in the synovium at an early stage of treatment. This project is led by Prof
FitzGerald and Dr Ursula Fearon in collaboration with the P.P. Tak group in Amsterdam, and S.
Pennington and M. Dunn of the Proteome Research Centre, UCD. Synovial tissue has been obtained
via arthroscopy at baseline and 1 month from a cohort of patients, half of whom were receiving
Adalimumab and half placebo injections, before beginning Adalimumab after 1 month. We are using
proteomics technology (2D- DIGE and mass spectrometry) to analyse the proteome of these synovial
tissue samples and identify differentially expressed proteins and potential biomarkers. These potential
biomarkers will then be validated using various molecular biology methods. A pilot study on a smaller
cohort has allowed us to optimise the experimental methodology and identify several interesting
proteins.
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