Chronic inflammation, a condition present in various diseases including those with an immune component, is an important cause of morbidity/mortality in the developed world. A wide range of disorders fall into this disease category. These are rare or common disorders, whose best management requires an integrated approach, tightly linking clinicians from internal medicine or medical specialties to research teams with translational research programs in the field.
The rationale for the i2B is principally based on:
- The concept of the autoinflammatory/autoimmune disease continuum (AADC)
Autoinflammatory syndromes were first defined as opposed to autoimmune disorders, as diseases characterized by systemic inflammation, in the absence of high-titer autoantibodies or antigen-specific T cells. Recent advances in the pathophysiology of autoinflammatory/autoimmune diseases have led to a reexamination of their nosology. It now appears that autoinflammatory and autoimmune diseases do not represent two distinct categories of disorders; rather, they form a disease continuum ranging from pure autoinflammatory disorders to pure autoimmune diseases, encompassing a large panel of inflammatory diseases with some autoimmune component, and vice versa (McGonagle 2006).
- The expected benefits of managing rare disorders together with common diseases
Studies on rare disorders are of particular importance as they can have a significant collective impact on the molecular bases, the pathophysiology and the treatment of common disorders.
Indeed, genes responsible for rare disorders can represent susceptibility loci for common inflammatory diseases. Also, expected results of research on rare diseases are important for a better understanding of the pathophysiology of common diseases, as they often represent a “model of dysfunction” severely affecting a limited number of biological pathways shared with common multifactorial conditions. Finally, some treatments that have proven effective in rare disorders are also used in more common diseases.
- The importance of the transition from pediatric to adult healthcare departments.
In chronic diseases, the importance of the transition from pediatric to adult healthcare departments has been clearly demonstrated. An important and original specificity of i2B is the tight connection between the unique pediatric hospital of Universite Pierre et Marie Curie (UPMC) and adult healthcare departments from neighboring establishments of the same university i.e Pitie-Salpetriere, Tenon and Saint-Antoine. Four departments of the Trousseau Hospital participate in i2B (the pulmonology, nephrology and neurology departments and the medical genetics unit) .
The i2B Consortium
I2B is a collegial network of 32 teams from 4 university hospitals (Pitie - Salpetriere, Saint - Antoine, Tenon and Trousseau) linked to the Universite Pierre et Marie Curie (UPMC).
These teams provide expertise in the biological and clinical aspects of inflammation, immunology, genetics, cell biology, systems biology and biotherapy. In addition, the complementary expertise of the 4 pediatric units (pneumonology, nephrology, medical genetics and neurology) and of the 9 departments of adult medicine (internal medicine, nephrology, gastroenterology, rheumatology, ophthalmology and pneumonology) cover the entire spectrum of the autoimmune autoinflammatory disease continuum (AADC).
I2B aims to strengthen existing links, stimulate new collaborations and promote cross-fertilization between disciplines so as to improve patient management.
Our general objective is:
to better study and manage inflammatory and autoimmune diseases by integrating translational information. This will allow breaking down some artificial boundaries between these disorders through the study of important phenotypes that cut across diagnostic groups. This should lead to reconsider current disease classification schemes in the light of the AADC seen through various arms of the immune system.
Our specific objectives are:
- to cross-phenotype inflammatory and autoimmune diseases,
- to discover and validate biomarkers and novel therapeutic targets,
- to develop and evaluate biotherapies based on this knowledge,
- to implement high-level teaching and training activities in the field.
Actions / Work Packages
The project is structured around 4 work packages (WPs):
- WP1: Patient care, Cohorts, Deep phenotyping & Clinical trials
WP leaders: P. Cacoub; A. Clement; G. Grateau
- WP2: Basic and translational research
WP leaders: S. Amselem; P. Ronco; P. Seksik
- WP3: Translational medicine and biotherapy
WP leaders: F. Berenbaum; D. Klatzmann; E. Rondeau
- WP4: Teaching and dissemination
WP leaders: O. Benveniste; J. Masliah; G. Trugnan
IMPACT ON PATIENT CARE
We expect a significant improvement in patient care through:
- Specific consultations for children to adult transition
- Multidisciplinary consultations which facilitate access of patients to the medical experts in the clinical departments of i2B
- Better phenotyping of the patients that will define novel groups/subgroups of patients that would benefit from personalized care
- The discovery of biomarkers with diagnostic and prognostic value
- The better use of existing biotherapies
- The development of novel biotherapies
- SOCIETAL IMPACT
A better diagnostic, classification, follow-up of patients, notably using biomarkers, should clearly translate into better disease management and thus improved quality of life for patients. Interactions with patient groups will also contribute to better information to patients and general public regarding the scientific outputs and therapeutic perspectives.
- INNOVATION AND ECONOMIC IMPACT
The new treatments to be developed, notably IL-2 a drug already on the market for which we pioneered the novel use at low dose, have the potential to revolutionize the treatment for a large variety of diseases of the autoimmune autoinflammatory disease continuum (AADC). In addition, validation of biomarkers, should provide novel hypotheses for research.
Therefore, the major economic impact will be:
- the economic consequences of an improved quality of life for patients
- the lower costs to the health systems for coping with less patients
- the wealth creation through results exploitation.