Regulating Rheumatoid Arthritis

Current therapies for rheumatoid arthritis (RA) successfully suppress disease
symptoms albeit often at the cost of side-effects such as infections.
Furthermore the underlying pathology of RA, immune deregulation, is not
restored by these therapies, often causing patients to remain on long-term
immunosuppressive medication. Novel cell therapy-based methods are being
developed with the aim of strengthening the patient*s natural immune regulation.
Such tolerogenic cell therapy methods involve the ex vivo training or
engineering of the patient*s own immune cells (tolerogenic dendritic cells
(tolDC) or regulatory T cells), which are subsequently injected back into the
patient. The hope is that cellular immunotherapy will reduce or completely end
the need for long-term use of immunosuppressive medication in these patients.
We have identified four challenges that in our opinion need to be addressed
before the efficacy of tolerogenic cell therapies for RA can be properly
tested.

The aim of this study is to better understand various prerequisites for the
development, implementation, and immunological monitoring of immune regulation
restoring therapies in RA patients. To meet this aim, the study is divided into
four equally important challenges with their corresponding objectives:
Challenge 1: Defining in- and exclusion criteria for tolDC therapy. In this
objective we will investigate the phenotype and functionality of tolDC
generated from peripheral blood of RA patients in comparison to those from
healthy individuals. We will study how the use of various types of
immunosuppressive medication and the disease activity affect the ability to
generate functional tolDC from peripheral blood of RA patients.
Challenge 2: Establishing assays for monitoring of antigen-specific T cell
responses in RA patients. In objective 2 we will develop assays for the
detection of antigen-specific regulatory T cell responses in support of
auto-antigen targeted immunotherapy clinical trials in RA.
Challenge 3: Identifying T cell receptor sequences for engineered Treg therapy.
In objective 3 we will identify and characterize antigen-specific T cell
receptors for auto-antigen targeted engineered Treg therapy strategies.
Challenge 4: Characterizing the metabolic signature of Treg from RA patients
and healthy controls. In objective 4 we will compare the metabolic signatures
of Treg of RA patients and healthy controls. This will provide insight into how
RA and current RA therapies affect Treg metabolic characteristics.

Observational cross-sectional study

Participants will undergo a physical examination (to determine disease
activity) and a single venepuncture (a maximum of 80 mL blood). Patients may
elect to participate multiple times, requiring renewed informed consent, but
never more than two times per year. As blood is primarily taken together with
routine blood sampling, no additional burden arises for the patient. The
participants of this study will not directly benefit from participation in this
study.