WP 4. Synovial tissue markers for prediction of outcome and of response to therapy

This area of work will be lead by Partner 6 (AMC Amsterdam) with input from, Partner 3 (Berlin-Charité), Partner 4 (Vienna), Partner 5 (Dublin) and Partner 27 (Arthrogen)

Synovial biopsy specimens have been collected for several years by the partners involved and stored as frozen specimens. Certain projects on standardisation have been performed between the involved research groups, but no general standards have been established as to methods to acquire and store these biopsies. Further, no databases have been established describing the content of these biobanks.

The present project will aim to use synovial biopsies in a much more multifaceted way than before, with the goals (outlined in B.4) of using molecular studies of synovial biopsies to characterise different molecular patterns in inflamed joints both longitudinally during the long-term course of RA, and before and after targeted therapies. When combined with sophisticated methods for cellular analyses (see other WPs), expression profiling and proteomics analyses, these analyses will be able to give a much better understanding of the relative importance of different molecular pathways in different patient subpopulations. These subpopulations of patients will also be defined by genetic means.

Two types of biopsy materials will be taken and be subject to analysis during the first 18 months:

•  Historic materials, taken by arthroscopy and stored as frozen biopsies. More than 500 biopsies exist at present within the partner groups. These biopsies will be characterised and assembled in a database, enabling better multicentre studies on a natural course of disease, as well as studies of effects of today's targeted therapies.

•  Prospective studies, where in particular new therapies will be evaluated using repeated biopsies. During the first 18 months we will establish this option by constructing a common protocol for obtaining biopsies and applying this protocol in a multicentre way for molecular evaluation of one of the presently available targeted therapies, most probably TNF-blockade. After having established the standards and the protocols and made this feasibility study, the system will be available for the evaluation of new targeted therapies (described in other parts of the programme), where biopsies taken during standardised procedures can be assembled and analysed by means of the technology described in other workpackages.