The ultimate goal of IMCIS is to improve patient´s quality of life and reduce socio-economical costs of inflammatory skin diseases (ncISD) by implementing the concept of individualised Medicine. That includes 1) identification of biomarkers predicting clinical Outcome or risk for comorbidities; 2) assessment of novel therapeutics; and 3) molecular diagnostics in the field.
IMCIS was successful and has achieved the following aims:
1. A cohort of more than 400 patients with several inflammatory skin diseases was built up. Of all patients, detailled clinical phenotyping and transcriptome data are uploaded to general databases. They build a unique data resource.
2. New disease ontology: We demonstrated that characterising patients with just a clinical diagnosis is insufficient - both to cluster patients according to the clinical phenotype as well as to explain the molecular variability in lesional skin. Thus, we need a more granular, ideally objective, way of describing ncISD patients (Lauffer at al, JID 2018; 1 under consideration, 1 in preparation).
3. Identifying molecular drivers of biologically relevant phenotypes: amongst ncISD, several biological processes are conserved, e.g. infiltration of neutrophil granulocytes or pathological broadening of the epidermis. These processes might occur within a given diagnosis, but might also be absent. We have developed a biocomputational pipeline to identify hidden molecular drivers of such processes within a heterogeneous dataset, the so-called AUGER approach (1 manuscript under consideration). Amongst others, AUGER has identified the transcription factor CEBPB a central for neutrophil biology. Further evaluations showed that the isoform Lip of CEBPB is associated with Th17 immunity and represents a promising therapeutic target (2 manuscripts in preparation).
4. Molecular diagnostics: Our first molecular classifier of NOS2 and CCL27 expression in lesional skin distinguishes Psoriasis from eczema. In a POC grant, we transferred this classifier to a medical device, a Point-of-care microfluidic disk System. The success of peLabDisk resulted in a award-winning start-up company, Dermagnostix (
https://www.dermagnostix.com/(s’ouvre dans une nouvelle fenêtre)). Through IMCIS, we have now established further classifiers, amongst them a classifier to distinguish venous ulcers from pyoderma gangrenosum or eraly lymphoma from eczema (2 manuscripts in preparation).
5. Prediction of natural course of disease: some ncISD patients experience a life-long severe inflammation, in others the clinical course is rather self-limited. Based on our approach, we identified clinical attributes as well as molecular markers that help to predict the natural clinical course of atopic dermatitis (Lauffer et al, Allergy 2021) as well a early response biomarkers to immunoadsorption therapy of atopic dermatitis (Thomas et al, J Invest Dermatol 2021).
6. Prediction of therapeutic outcome: Before IMCIS, there was no way to predict the therapeutic outcome at an individual patient´s level. As a proof of principle, we have shown that one hallmark of several inflammatory and autoimmune Skin diseases, the so-called interface Dermatitis, is caused by type 1 lymphocytes that induce keratinocyte necroptosis (Lauffer et al, JID 2018). These type I immune cells can be targeted e.g. by JAK Inhibitors, thus there is a high translational value in the mechanistic isnights (Seiringer et al, Acta DV 2020). Currently, we validate molecular classifiers to predict the therapeutic response to methotrexate or to IL-17 inhibitors, respectively (2 manuscripts in preparation).
