LAUSR

Based on the synchroneity of severe infections, multiple autoimmune disorders, atopic dermatitis, chronic diarrhoea and insufficient weight gain, the “immunodysregulation, polyendocrinopathy, enteropathy, X-linked” (IPEX) or IPEXlike syndrome was first suspected at the age of 8 in 2015, and calcineurin inhibitor tacrolimus was introduced [1]. IPEX syndrome is a rare primary immunodeficiency syndrome characterized by the development of multiple autoimmune disorders. IPEX is caused by mutations in the forkhead box protein 3 gene (FOXP3), which encodes a key transcription factor required for regulatory T cell (Treg) development, maintenance and function [2]. In addition to the traditional clinical presentation (severe enteropathy, type 1 diabetes and skin lesions), IPEX may include other variable and distinct clinical manifestations [3]. The coding region of FOXP3 was analysed by Sanger sequencing and a silent mutation was detected (c.816G > A). To assess the potential effect of the mutation on RNA splicing, RNA of peripheral white blood cells was tested and the skipping of exon 7 was observed; thus, the effect of the mutation was p.Leu246fs*160 [4]. Treg cell dysfunction is the main pathogenic event leading to multiorgan autoimmunity in IPEX [3]. Functional data demonstrate that Treg cells isolated from IPEX patients are dysfunctional, as they cannot inhibit proliferation and cytokine production of autologous or allogenic T effector cells [3]. Our patient had typical (enteropathy, skin lesions, severe infections) and atypical (non-lupus full-house nephropathy) symptoms without type 1 diabetes leading to the diagnosis of IPEX. Treg cell count was at the lower limit of normal range (CD3 + /CD4 + T cell count 503 cell/μL (lower limit of normal 300 cell/μL), 4.6% Treg cells of the CD3 + / CD4 + cells (normal range 4–9%)). Treg cell subpopulations and intracellular cytokine production were not evaluated and functional T cell tests were not available at the time of diagnosis.