Characterising the clinical phenotype and immunopathophysiology of food protein-induced enterocolitis syndrome in Australian children

Abstract

FPIES is an uncommon food allergic disorder in infants and children. It differs clinically from IgE-mediated food allergy presenting acutely with delayed profuse vomiting, at times with lethargy, pallor, floppiness and diarrhoea. The diagnosis is difficult as it is based on clinical criteria, with no diagnostic test aside from oral food challenge. There is geographic variation in demographic features and the immunopathophysiology of FPIES is largely unknown. In this thesis, a retrospective study was undertaken to characterise the demographic and clinical phenotype of FPIES in Australian children. Prospective epidemiological and mechanistic studies involving time to resolution, whole blood mRNA profiling and flow cytometric analysis of monocytes and innate lymphoid cells (ILC) were performed to evaluate potential immune mechanisms underpinning FPIES. Here, we demonstrate that rice is the most common food trigger in Australia. Cross-reactivity was commonly seen between rice and oats; and cow’s milk and soy. Children with rice and cow’s milk FPIES achieved resolution at an earlier age compared to those with egg and fish FPIES. Comparison of clinical presentations of children with FPIES, bacterial sepsis or infectious gastroenteritis demonstrated that the absence of fever and normal C-reactive protein was more likely in FPIES. mRNA expression analysis showed upregulation of innate immunity, particularly granulocyte adhesion and triggering receptor expressed on myeloid cells 1 (TREM1) signalling. Flow cytometry demonstrated increased TREM1 expression on classical monocytes in persistent FPIES. Downregulation of B7 integrin in ILC1 was seen, suggesting that ILCs may play a role in regulating tolerance. This data furthers our understanding of FPIES, with a characteristic demographic and clinical profile in Australian children. Although not yet fully understood, preliminary findings suggest that innate immune mechanisms have a key role in the immunopathophysiology of FPIES.