Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - RACE (Rheumatoid Arthritis Caught Early: investigating biological mechanisms preceding chronification of joint inflammation to identify patients prior to presentation of classic chronic arthritis)

Teaser

Overall aim.Rheumatoid Arthritis (RA) causes long lasting disability. At the time of clinically evident arthritis and diagnosis, the disease is already persisting, requiring long-term suppressive treatment. The overarching aim is to prevent chronic arthritis and RA by...

Summary

Overall aim.
Rheumatoid Arthritis (RA) causes long lasting disability. At the time of clinically evident arthritis and diagnosis, the disease is already persisting, requiring long-term suppressive treatment. The overarching aim is to prevent chronic arthritis and RA by inhibiting the evolving auto-immune response in a pre-arthritis phase. Currently, identification of RA-patients before the classic presentation with clinically evident chronic arthritis is beyond the state of the art. This project aims to achieve this early recognition by increasing the mechanistic understanding of pre-arthritis phases.

Impact for society.
The ability to identify patients with imminent RA in a disease phase in which chronicity is not yet established allows very early intervention and the ability to prevent the development of chronic RA. At present RA is an important cause of functional loss, work loss and associated with high costs for society by the long-term use of expensive treatment (biologics). Prevention of disease chronicity will likely reduce the level of RA-related work loss and prevent or diminish the long term need of expensive therapies.

The project.
The project will study RA-specific auto-immune responses at the cellular and humoral level as well as markers reflecting local and systemic inflammation. Serial data collected over time will be combined to reveal interactions between markers and time relationships. Additionally a prediction model identifying imminent RA will be developed. This project is based on recent work on progression from Clinically Suspect Arthralgia (CSA; the symptomatic phase preceding clinical arthritis) clinical arthritis and RA.

Work performed

The longitudinal cohort of patients that presented with CSA and that are followed on the development of clinical arthritis and RA has expanded and now includes >650 patients.
Novel autoantibody characteristics are being studied, among which aberrant ACPA-F(ab)glycosylation. Novel autoantibody reactivitites are being measured. The imaging studies done so far revealed a novel feature (tenosynovitis at the level of small joints) that is highly predictive of RA development and that seems to be one of the first features of joint inflammation. This finding changes the concept of RA, as it was always considered as an exlusive disease of synovitis. The present data show that tenosynovitis and synovitis precede the development of osteitis and early clinical arthritis. Altogether RA development fits the ‘outside-in hypothesis’, and not the ‘inside-out’ hypothesis. A computer-aided image analysis system to detect subclinical tenosynovitis on MRI is being generated.

Final results

This project is feasible, thanks to unique ‘pre-RA’ cohorts and cross-boundary work done with basic scientists, clinicians and engineers. In the end, the work with different disciplines on material of the same patients will be integrated and translated to the clinic. It is foreseen that this multidisciplinary and intersectorial project will open new horizons for preventive, targeted interventions in (imminent) RA.