Rationale

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

Objectives

Our general objective is:

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