The gastrointestinal immune system has evolved to avoid and counteract the invasion of pathogens. To allow a strong inflammatory immune response during infection but avoid tissue damage there is a need for effective immune regulation. Defects in immune regulation lead to immunopathology such as inflammatory bowel disease or celiac disease.
About one fifth of all patients with IBD present with initial symptoms during childhood and adolescents. In particular in the very young children patients an underlying immunodeficiency may cause IBD-like symptoms. The analysis of immune deviation in children with IBD and IBD-like symptoms may contribute to the understanding of the complex puzzle of molecular mechanisms involved in IBD.
To investigate novel genetic defects to lead to very early onset intestinal inflammation we established the COLORS in IBD study (COLitis of early Onset - Rare diseaseS withIN IBD). COLORS in IBD has several international collaborators. In collaboration with the Sanger Center Cambridge and the Wellcome Trust Center of Human Genomics (WTCHG) Oxford we investigate patients with pediatric onset of IBD using next generation sequencing.
A further area of interest is the immune response in patients with defects in the PI3K signalling pathway. One large group of patients with defects in this pathway have mutations in the phosphatase PTEN. Due to heterozygous mutations in the PTEN gene patients develop the PTEN hamartoma tumor syndrome which includes Bannayan Riley Ruvalcaba syndrome and Cowden's syndrome. We investigate the functional consequences of PTEN deficiency for the development of the mucosa associated lymphoid tissue, B and T cell responses.
Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome
Béziat V. et al, (2020), Journal of Experimental Medicine, 217
COVID-19 and Paediatric Inflammatory Bowel Diseases: Global Experience and Provisional Guidance (March 2020) from the Paediatric IBD Porto group of ESPGHAN.
Turner D. et al, (2020), Journal of pediatric gastroenterology and nutrition
Absence of GP130 cytokine receptor signaling causes extended Stüve-Wiedemann syndrome.
Chen Y-H. et al, (2020), J Exp Med, 217
Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.
Serra EG. et al, (2020), Nature communications, 11
Prevalence and Clinical Features of Inflammatory Bowel Diseases Associated With Monogenic Variants, Identified by Whole-Exome Sequencing in 1000 Children at a Single Center.
Crowley E. et al, (2020), Gastroenterology