Disease background and the importance of biomarkers
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that mainly affects the peripheral joints of the skeleton, in particular the joints of hands and feet. Chronic synovial inflammation activates tissue destructive pathways leading to cartilage and bone damage (erosions). Inflammation and destruction cause pain, joint swelling and loss of function. Sustained or uncontrolled disease leads to permanent damage and progressive invalidity.
RA is a complex disorder to which both genetic and environmental or acquired factors contribute. Recent data indicate that autoimmune diseases such as RA do not represent a single entity but most likely a spectrum of disease subtypes with shared and distinct immunopathogenic mechanisms. Therapies may therefore have to be tailored for a given subtype or even at the personal level. This concept and approach requires assays to screen patients and classify them according to their disease subtype, projected disease course and expected response to therapy. Moving towards this personalized medicine concept requires novel biomarkers.
Aims of the RA research platform
The CMI RA research platform consists of several academic and clinical partners, distributed over Flanders:
- UHasselt - Prof. Somers, Prof. Stinissen, Prof. Geusens, Prof. Noben
- UZ/KULeuven - Prof. Verschueren, Prof. Westhovens, Prof. Lories, Prof. Luyten
- UZ/UGhent - Prof. Elewaut, Prof. Jacques, Prof. van den Bosch, Prof. Deforce
- UZ/UAntwerpen - Prof. De Clerck
The CMI RA research platform aims to develop new tools and novel biomarkers using state-of-the-art technological tools for biomarker discovery and validation in early RA. These technologies will be used to identify biomarkers associated with (1) early diagnosis of disease, more specifically in RF/ACPA negative (seronegative) patients (2) disease remission, (3) bad prognosis at treatment initiation and (4) response to therapy.
The strength of the RA platform is based on the combination of the technological expertise present at the CRCs and the use of the RA-biobank, consisting of a collection of samples of DNA, blood and disease-related tissues and the corresponding clinical data. This collection is currently being expanded by the MarkeRA registry, a set of well-defined, prospective samples in a close coordination between the CRCs. The set of patient samples, collected longitudinally throughout the disease course, and careful monitoring of corresponding patient data on disease progression, treatment response and induction of remission will allow the discovery of novel biomarkers with diagnostic, prognostic and theranostic potency.
Different, complementary biomarkers will be screened for using a series of different technologies.
- Autoantibody-associated antigens will be identified by systematic profiling of the humoral immune response using phage display technology.
- Proteins differentially expressed in RA serum will be identified using mass spectroscopy.
- Genetic and epigenetic markers will be identified by genome-wide analysis of SNPs in the genetic material and miRNAs in the serum
The tools and biomarkers identified in this project will contribute to better and earlier diagnosis of rheumatoid arthritis, the accelerated achievement of disease control or remission as early as possible after disease initiation and improving a treat-to-target strategy using validated outcome measures.