WP3 - Mechanisms of Immune Tolerance

Objectives

The aim of WP3 is to elucidate critical immune reactions driving chronic rheumatic inflammation and thereby define novel targets and pathways which could contribute to the therapeutic establishment of immune tolerance, and thus novel targets of therapy. The immune system of healthy individuals, at-risk individuals, patients with early RA and established RA, and patients in therapy-induced and spontaneous remission will be analysed in molecular detail for autoantigen and modified autoantigen profiles, autoantigen-specific cells and for a systemic imprinting impacting on the restoration of tolerance.

The specific objectives are:

1. Identification of relevant (auto)antigens driving the adaptive immune response in various subsets of RA patients, from healthy individuals with genetic, serological and environmental risk factors to individuals with various autoimmune reactions (without symptoms) to individuals with arthralgia and other symptoms preceding joint inflammation until presence of fully developed RA.

2. Identification of cells and mechanisms that contribute to disease development, progression, and maintenance, as well as those counteracting disease development and those blocking restoration of tolerance.

3. Characterisation of the functional and epigenetic systemic imprinting of the immune system in individuals at the various stages of RA.

Partners

• KI

• DRFZ (lead)

• MUW

• UoB

• UNEW

• UGLA

• LUMC

• UQ

• SE

• ANOCCA

• IRB

• Janssen (lead)

• UCB

• GSK (lead)

• Sanofi

• BMS

• PFIZER