Clinical and immunological characteristics of five patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome in China–expanding the atypical phenotypes

Abstract

BackgroundImmune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder of the immune regulatory system caused by forkhead box P3 (FOXP3) mutations. Abnormal numbers or functions of regulatory T (Treg) cells account for the various autoimmune symptoms. We aimed to explore the molecular genetics and phenotypic spectra of patients with atypical IPEX syndrome in China.MethodsWe analyzed the molecular, clinical and immune phenotype characteristics of five Chinese patients with FOXP3 mutations.ResultsWe summarized the molecular and phenotypic features of five patients with FOXP3 mutations, including two novel mutations. Four of the five patients displayed atypical phenotypes, and one developed immune-related peripheral neuropathy. Three of the five patients showed normal frequencies of Treg cells, but the proportions of subsets of Treg cells, CD4+ T cells and B cells were out of balance.ConclusionsOur report broadens the understanding of the clinical features of atypical IPEX syndrome. Our detailed analyses of the immunological characteristics of these patients enhance the understanding of the possible mechanisms underlying the clinical manifestations.

FOXP3 deficiency, from the mechanisms of the disease to curative strategies

“…Consistent with these normal levels of IL‐17, the frequency of Th17 cells was not elevated in most of the patients, the exception being a few with typical and early onset IPEX. Recently, variability in Th17 cell frequencies has been shown in a group of three IPEX patients 34 . These data tend to contrast our own findings, as well as those of other groups 26,31,32 .…”

“…Recently, variability in Th17 cell frequencies has been shown in a group of three IPEX patients. 34 These data tend to contrast our own findings, as well as those of other groups. 26,31,32 However, the following experimental evidence sheds light on these apparent discrepancies in the different patients and across the different studies.…”

Case Report: Eosinophilic gastritis with pyloric stenosis in immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

“…Luo et al reported a case of IPEX carrying the same mutation that presented with metaplastic atrophic gastritis and villus atrophy in the descending part of the duodenum ( 20 ). There have been several cases of eosinophilic esophagitis reported in IPEX syndrome ( 21 ) as well as at least two patients with pyloric stenosis described by Fang et al ( 22 ), but it is rare to see chronic gastritis with eosinophilic infiltration ( 23 ). In this report, we described an atypical IPEX case presenting with severe gastritis and pyloric stenosis.…”

Infections in Disorders of Immune Regulation

“…A comprehensive study of 96 patients with IPEX showed a classical triad of type 1 diabetes, eczema, and enteropathy as the most common manifestations. Apart from the classical triad, other manifestations include failure to thrive, alopecia, dermatitis, arthritis, autoimmune pancreatic exocrine insufficiency, gastritis, kidney disease, interstitial lung disease, and infection [ 25 , 26 ]. Table 3 summarizes the studies reporting infections in patients with IPEX syndrome.…”