EAPS 2014 Conference Chaser Day 1
The first plenary talk was not a game changer for us general paediatricians, but it definitely deepened my appreciation of the complexity immunity. Yes, I now feel like I know even less about our immune systems than before – can it can any more complicated?)
The satellite events have finished and this evening at the official opening Professor Jean-Laurent Casanova (from Rockerfeller University, but with research laboratories in both Paris and New York – link here for a better outline and bio) outlined his understanding of the complex genetic determinants of individuals’ vulnerability to infectious disease.
He began with an interesting historical overview of our scientific theoretical approach to children with fever, passsing from Pasteur and germ theory through to his own current work, but resonating with the postulate of Archibald Garrod:
“It is, of neccesity, no easy matter to distinguish between immunity which is innate, and that which is acquired”
Beginning from an awareness of the Mendelian basis for some serious genetic vulnertability to infection (eg agammaglobulinaemia as an AR, fully penetrant primary ImmDef), our current understanding as informed by Prof Casanova’s work and his collaborators, has demonstrated that single gene deletions can give rise to very particular immunophenotypes, with very particular disease susceptibilities eg UNC-93B deletion causing TLR dysfunction in oligodendrocytes makes these cells vulnerable to HSV, and this particular immunophenotype (constituted by various gene defects) accountsd for at least 25% of Herpes Simplex Encephalitis in infants and children.
Prof Casanova also described unpublished research regarding a unique gene deletion leading to particular vulnerability to serious influenza infection.
His concluding statement (stated as if it was a belief) was; “each child is unique. Every child has a singular disease.”
He postulated the ramifications of these realisations of cellular, molecular and genetic bases of infectious disease as being an improvement in our ability to prognosticate and counsel families, and perhaps to generate cytokine specific interventions.
These seemed like big ideas to me, and it seems as if there is a lot more work to be done to detail our understanding of the many different ways in which our immune systems can be vulnerable.