Funny old word – means “without place” in Greek, which refers to the fact people didn’t know what was going on with these kids – not the mechanism, not a particular infection, not a specific organ or system.
Some clues from genetic mutations – JAK1 mutations are a cause of severe atopy and eosinophilia. Involved in IL-4, IL-13, and IFN signaling. Long-term ruxolitinib (kinase inhibitor) treatment of 2 children carrying the JAK1GOF (p.A634D) variant improved their growth, eosinophilia, and clinical features of allergic inflammation.
The idea of the immune system being about defence is wrong! Tolerance is everywhere! B and T regulatory cells keep everything under control.
Microbiome in atopic conditions different, and differences can precede disease.
Neonatal gut microbiome predicts sensitisation (3 groups). Main differences are bifidobacteria and enterobacteria. Differences are related to maternal diet, delivery method, feeding method, antibiotic exposure etc. Cumulative effect. Still apparent at age 3.
Breast milk contains 1/3 oligosaccharides that are not digestible by baby! Designed for microbiome!? Some genetic variations. Oligosaccharide composition associated with later sensitization.
Short chain fatty acids eg butyrate associated with sensitization – yogurt! Component of soluble fibre! Affect T reg cells.
Morganella morgani produces histamine! Higher levels in asthma, esp higher risk.
[Liam O’Mahony – Cork, prev Davos]
Karelia study – biodiverse environments eg forest and agricultural had greater diversity of skin microbiota cf urban, shore. Inversely related to atopy, and IL10 expression. [Finland now has national programme for allergy prevention]