TIMID

The current treatment regimens for these diseases are associated with therapy failure, side effects and comorbidities. To improve management there is an urgent need for precision medicine targeting the underlying pathogenic immune response that is driving disease.

One of the key features shared by multiple IMID is an incessant inflammatory T-cell response that drives disease. T-cell driven IMIDs have many overlapping immunological features, a common genetic background and share treatment modalities. The TIMID consortium proposes to generate a new IMID taxonomy independent of the diseased organ but based on the pathogenic immunological mechanisms driving disease.

We hypothesize that a faulty immune response to intestinal bacteria is an important driver of disease in these patients. In our partnership of 6 academic institutions and 5 companies, we will unravel the common cellular basis for seven IMIDs. We will analyze the deregulated anti-microbial immune response and classify these IMIDs on the basis of this immune response. These results will empower more precise treatments using existing drugs and identify new targets for future drug development.

By combining cutting edge technology with unique in depth characterization of immune cells from pediatric and adult patients and sharing knowledge and clinical expertise, this consortium will uncover fundamental processes in the pathogenesis of IMIDs. Through in silico modelling of the emerging large datasets the consortium aims at generating a classification on the basis of defective immune response that predicts disease severity and therapy responsiveness. As such, the consortium aims to improve treatment of IMID in the near future by realizing precision medicine geared at treating the patients’ individual disease as effectively as possible with as few side effects as possible.

What have we achieved so far?

1. Disease-specific TIMID immune profiles using peripheral blood mononuclear cells and intestinal biopsies discriminate subgroups of patients with distinct disease course and response to therapy.
2. Proteomic profiles of 92 proteins in 3792 serum/plasma samples from 15 TIMID cohorts 1) identify common and discriminative protein profiles across TIMIDs and are used to 2) classify disease severity and response to therapy within each disease.
3. Approximately 10.000 fecal microbiome samples have been sequenced to uncover the microbiome signature of inflammatory diseases, including IBD, celiac disease, rheumatoid arthritis and type 1 diabetes. In the past year, these data have been analyzed and extrapolated to identify changes of abundance at a bacterial species level that are commonly seen in all TIMID.
4. To identify altered immune responses to these species, the species were cultured and will be used to generate a microbial host fingerprint using a high throughput serum/ plasma immunoglobulin reactivity assay and identify species specific T-cell responses in relation to the immune peripheral blood profiles.

For more information visit the TIMID website.

Collaborators