PID 2.0 - Project
The basis for our immune system defense lies in the detection of foreign enitties like viral nucleic acids and the action of type I interferons (IFN) as essential communication molecules. When the IFN system is underactive (Type I IFN deficiencies), the immune system doesn't function properly. Patients are more vulnerable for infections, associated with severe morbidity and mortality. Conversely, over-active type I IFN signaling has been identified as a critical driver in both monogenic diseases (e.g.interferonopathies) and autoimmune diseases (e.g. systemic lupus erythematosus). Furthermore, dysregulation of type I IFN signaling is being identified in a growing list of rare diseases. These clinical observations underscore the pivotal role of IFN signaling across a broad spectrum of human diseases, spanning clinical immunology, rheumatology, pneumology, infectiology and neurology both in children and adults.
A number of treatments targeting the type I IFN pathway have entered clinical practice. Recombinant type I IFN is a validated treatment in autoimmune diseases. Furthermore, clinical trials evaluating JAK inhibitors in type I interferonopathies have reported promising results. This suggests that manipulating the type I IFN pathway, whether by enhancement or inhibition, holds great promise as a therapeutic approach. Despite these therapeutic options being readily available in clinical settings, the rapid and accurate diagnosis of dysregulated type I IFN signaling remains a challenge. This unmet medical need is critical, with approximately 95% of patients suffering from severe viral infections and nearly 50% of those with undifferentiated autoinflammatory and autoimmune disorders remaining undiagnosed.
In the previous Grand Challenge program on Primary Immune Deficiencies, the mRNA based 'interferon score' test was developed and successfully implemented in the diagnostic workup of a small cohort of patients in a research setting. This validation project, PID 2.0, aims to further develop the ‘interferon score' into a clinical-grade diagnostic test and incorporate this tool into the clinical assessment for patients suspected of dysregulated IFN signaling. The diagnostic utility of this novel test will be investigated across different patients with distinct disease presentations, both on a national and international level. This advancement seeks to improve early diagnosis and guide targeted treatment strategies to enhance patient outcomes.
The goals of this proposal are threefold:
- Development of a clinical grade test: Further advance the technical development, and analytically and clinically validate 'the interferon score', accompanied by standard operating procedures for quality control and assurance. By the end of the project, this clinical grade test will be transferred to selected BELAC accredited laboratories and collaborating European centers.
- Evaluate the utility of the ‘interferon score’ test: The diagnostic utility of the ‘interferon score’ test will be evaluated in both national and international patient cohorts suspected of having inappropriate type I IFN signaling.
- Monitor impact on patients’ health: Selected patients identified with an aberrant ‘interferon score’ and confirmed clinical diagnosis will be offered timely access to recombinant type I IFN therapy or JAK inhibitors. Using a combination of registries, established disease specific tools and clinical parameters, we will monitor impact on patients’ health and by correlating with ‘interferon score’ results during treatment, we will evaluate the potential theragnostic utility of the ‘interferon score’.