Lethal infectious diseases of childhood: Single-gene inborn errors of immunity ? Jean-Laurent Casanova Head, St. Giles Laboratory of Human Genetics of Infectious Diseases Pediatrician, Necker Hospital for Sick Children, Paris, France Professor, The Rockefeller University, New York, USA
1911-1917: The discovery of inapparent infections Only 10 -7 to 10 -1 infected individuals develop clinical disease Microbes are necessary but not sufficient to cause disease Even in the course of primary infections … What accounts for inter-individual variability ? What is the pathogenesis of infectious diseases ?...
Puberty Single-gene defects Age Polygenic/Complex predisposition 100% Genetic cases of life-threatening infections Primary infection Secondary infection/Reactivation Life-threatening infections of childhood: Single-gene inborn errors of immunity?
New targets: fulminant viral hepatitis, acute viral myocarditis, etc.
New technologies: deep sequencing, stem cells, etc.
Conclusions and perspectives
Pioneers and leaders in the field of human inborn errors of immunity
Aim: dissecting the molecular basis of host defense in natura
The genetic theory: the new frontier in infectious diseases
Aim: understanding the pathogenesis of infectious diseases (at last)
Selected references: Altare et al. , Science 1998; de Jong et al. , Science 1998; Dupuis et al. , Science 2001; Picard et al. , Science 2003; Casrouge et al., Science 2006; Casanova and Abel, Science 2007; Zhang et al., Science 2007; von Bernuth et al. , Science 2008; Puel et al., Science 2011.