Primary immune deficiency diseases (PIDs) are a heterogeneous group of life-threatening genetic disorders of the innate and adaptive immune system. To date there is still a lot of under-diagnosis as PIDs are very complex, rare (1/2.000 to 1/100.000 in Caucasians) and can present clinically in many forms. A large number of PID patients remain undiagnosed or get a label of undefined PID, preventing design of rational therapy. PID can lead to increased susceptibility to severe and/or recurrent infections and malignancy, which can easily be diagnosed by specialized centres, or to immune dysregulation with resulting auto-inflammatory diseases related to excessive innate immune activation and auto-immunity. The latter are much harder to diagnose and manage.
Therapeutic options are still limited due to lack of molecular insight. This places a heavy burden not only on patients and families, but also on health care systems.
The VIB-GCP PID-consortium will address the urgent need for mechanistic understanding and molecular diagnostic tools to better stratify PID patients and guide therapeutic decisions in the clinic. Additionally, research of novel targeted therapeutic concepts based on deep insight in the core immunological and molecular mechanisms driving specific PID will expand therapeutic options available to physicians and their patients. Not only will this have important and immediate impact on the life of affected patients, it will also have tremendous scientific impact in reverse translational research.
The project consortium concentrates on:
- Innovative biomarkers: standardized high-throughput screening of potential PID patients combined with immunophenotyping and whole genome genetic analyses to detect rare or novel PID disorders.
- Innovative treatments: establishment of reliable and powerful methods to generate patient-specific laboratory model systems (cellular and mouse), to utilize these patient-specific model cells to test innovative patient-specific treatments (e.g. drug re-purposing).
Facts & Figures
Precision medicine will be improved by translating innovative molecular diagnostic paradigms into clinical practice.
Adrian Liston • Stéphanie Humblet-Baron
KU Leuven-UZ Leuven
Contribution to the project
The PID VIB-GCP projects assembles expertise from the VIB Inflammation Research Center and the clinical acumen of pediatric and adult internal medicine specialists with proven track records in PID at KULeuven, UGent and UAntwerp (Profs. Meyts, Haerynck and Lambrecht, Schrijvers).
Proper laboratory diagnostics (TREC screening, immunophenotyping, functional immune assays) will be performed in university hospital clinical biology and hematology labs at KULeuven (Xavier Bossuyt) and UZGent (Jan Philippé). The labs of Prof. Liston, Prof. Meyts and the genetics lab of Prof. Elfride de Baere have access to next generation sequencing technology necessary for in-house analysis of suspect PIDs.
The testing and validation of novel biomarkers in PIDs will depend on the expertise in unsupervised analysis of high-dimensional data of both fundamental immunologists and bio-informaticians at VIB. Functional validation and trialling of personalized medicine using model systems and cutting-edge genomic engineering will take place both in the VIB fundamental molecular biology and immunology research labs of Prof. Beyaert, Prof. Liston and Prof Guilliams and the translational research labs of Prof. Haerynck and Prof. Meyts.
Core facilities involved
VIB's singularity platform is involved as an R&D partner, our Flow core, Transgenic core facility, Transgenic mouse facility and Bioimaging core are involved as service providers.
The objective of the VIB-GC program is to significantly increase the societal impact of VIB, hence taking its scientific leadership to the next level of global visibility, strategies between partners towards sharing of capabilities (samples, data, infrastructure) are prerequisite and motivated within the VIB GCP, aligned with the general principles of RRI and the Open Science policy of VIB in particular.
Close collaboration with the central biobanks in the partner institutions:
The development and practical implementation of this new knowledge will expand therapeutic options available to physicians and their patients. Not only will this have important and immediate impact on the life of affected patients, it will also have a tremendous scientific impact on reverse translational research. The project consortium concentrates on two main goals: - innovative biomarkers: standardized high- throughput screening of potential PID patients combined with immunophenotyping and whole genome genetic analyses to detect rare or novel PID disorders - innovative treatments: establishment of reliable and powerful methods to generate patient-specific laboratory model systems to test innovative patient specific treatments (e.g. drug re-purposing).
Jan Phillipé, UZ Gent, highlights another aspect of the social impact plans that are part of this project:
“With government support, we will also endeavor to set up a PID screening program for newborns in Belgium.”