High levels of IgE and/or eosinophilia are also found in patients with monogenic disorders caused by defects in FOXP3, IL2RA, IKBKG, WAS, or DOCK8 ( Table 2

and Supplementary Table 1). It should also be standard practice to exclude infectious causes such as bacteria (Yersinia spp, Salmonella spp, Shigella spp, Campylobacter spp, Mycobacterium Wnt inhibitor tuberculosis, Clostridium difficile), parasites (Entamoeba histolytica, Giardia lamblia), and viral infections (cytomegalovirus or human immunodeficiency virus), remembering that some infections can mimic IBD. However, most of these pathogens do not cause bloody diarrhea for more than 2 to Nivolumab clinical trial 3 weeks. In addition, monogenic disorders (such as B- or T-cell defect immunodeficiencies or familial HLH type 5, caused by STXBP2 deficiency) predispose patients to intestinal infections. 69 Celiac disease should be considered as a differential diagnosis for patients with suspected autoimmune enteropathy

presenting with villous atrophy (such as IPEX or IPEX-like patients). To detect possible causes of monogenic IBD-like immunopathology, we propose additional laboratory screening for all children diagnosed before 6 years of age. The limited set of laboratory tests includes measurements of IgA, IgE, IgG, and IgM; flow cytometry analysis of lymphocyte subsets (CD3, CD4, CD8, CD19/CD20, NK cells); and analysis of oxidative burst by neutrophils (using the nitro blue tetrazolium test or flow cytometry–based assays such as the dihydrorhodamine fluorescence assay). When placed in the context of clinical, histopathologic, and radiological data, these tests can guide the diagnosis toward the more prevalent defects of neutrophil, B-cell, or T-cell dysfunction. Pomalidomide Further tests are necessary to characterize particular subgroups,

such as those who develop the disease when they are younger than 2 years of age, those with excessive autoimmunity, or those with severe perianal disease. Those tests include flow cytometry analysis of XIAP expression by lymphocytes and NK cells129 and 130 or FOXP3 expression in CD4+ T cells, which can diagnose a significant proportion of patients with XLP2 and IPEX. Flow cytometry can detect functional defects in MDP signaling in patients with XIAP deficiency. 131 IL10RA and IL10RB defects can be detected by assays that determine whether exogenous IL-10 will suppress lipopolysaccharide-induced peripheral blood mononuclear cell cytokine secretion or IL-10–induced STAT3 phosphorylation. 30, 103 and 107 Increased levels of antibodies against enterocytes can indicate autoimmune enteropathy, in particular in patients with IPEX.