Tran et al.36 discuss a patient with a deletion that encompasses CTLA4 as well as ICOS, presenting with very-early-onset [VEO]-IBD unresponsive to conventional therapy.36 Biallelic mutations in the ICOS gene cause a deficiency that is characterised by nearly absent class-switched memory B cells; this leads to recurrent infections and autoimmune pathologies including IBD.58 The development of VEO-IBD in this patient could be evidence of the causative CTLA4 deletion, with additional effects of the compound ICOS deletion resulting in a more severe IBD phenotype. This evidence concerns the gene CTLA4 and infection.