Dissecting cause and consequence of the IFN signature in systemic autoimmune diseases

Systemic lupus erythematosus (SLE), primary Sjogren*s syndrome (pSS), systemic
sclerosis (SSc) and rheumatoid arthritis (RA), are systemic autoimmune diseases
that have unique as well as common immunopathological features. These include
activation of T cells and B cells that invade the target organs mediating
inflammation and producing disease-specific as well as disease-overlapping
autoantibodies. In addition, activated monocytes, myeloid and plasmacytoid
dendritic cells have been identified as key players in these processes. One
common and important denominator of the inflammatory mechanisms leading to
pathological changes in all these systemic diseases is the interferon (IFN)
signature. The triggers and the cell types or molecular pathways involved in
the induction of this IFN signature are essentially unknown. Importantly, also
the relation to the different disease phenotypes and disease course has not
been elucidated. Recent data suggest that multiple hits might be necessary to
elicit the cellular and molecular patterns as well as different disease
phenotypes, warranting a broad evaluation over a longer period of time to find
these multiple hits. Applying a systems biology approach, where data are
collected from all the components of a biological system, analysed and
integrated in order to generate a mathematical model, this broad evaluation
becomes feasible and can be used to elucidate the complex interaction of all
factors contributing to the above mentioned diseases.
In the department of Rheumatology and Clinical Immunology substantial cohorts
of SLE, pSS, SSc, RA and patients with primary anti-phospholipid syndrome
(PAPS) are treated, which constitutes a unique setting worldwide. This offers
an exceptional chance to assess the differences and similarities of such
complex diseases.

To identify new biomarkers for the prediction of disease outcome, resulting in
the identification of prognostic tools and markers to monitor treatment
response. Furthermore, the underlying pathways in systemic autoimmune diseases
shall be evaluated, which will lead to the discovery and characterization of
new therapeutic targets. To this end molecular profiles of biological fluids,
faeces, and of blood mDCs, pDCs (rare cells), B cells, monocytes and T cells
will be compared to each other and to healthy controls using the systems
biology approach.

Observational, cross-sectional and longitudinal study.

Participants will undergo a venipuncture (max 80 mL blood) max 3 times per
year, as part of a five year follow up to predict disease outcome. The
participants of this study will not directly benefit by participation in this
study.