Abstract
Background
Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) disorder is an autoimmune disease caused by loss-of-function mutations in the gene encoding the forkhead box P3 (FOXP3) transcription factor. These mutations affect the normal function of circulating regulatory T cells. IPEX is characterized by profound immune dysregulation leading to dermatitis, enteropathy, multiple endocrinopathies and failure to thrive. Different forms of renal injury have also been noted in these patients but these have been described to a very limited extent.
Case–Diagnosis
Three patients with IPEX with characteristic renal findings and mutations in FOXP3, including one novel mutation, are described. Case presentations are followed by a review of the renal manifestations noted in IPEX and the range of therapeutic options for this disorder.
Conclusions
We recommend that IPEX be considered in the differential diagnosis of young children who present with signs of immune dysregulation with a concomitant renal biopsy demonstrating immune complex deposition in a membranous-like pattern and/or interstitial nephritis.
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Acknowledgments
T.A.C. was supported by the National Institutes of Health grant R01AI085090
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All studies reported in this manuscript were performed in accordance with the Declaration of Helsinki.
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Alternative spelling of this author’s name is Yury Sheykin
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Supplemental Figure 1
Skin biopsy findings in case 1. a, b Hematoxylin/eosin-stained images showing low power and high power view, respectively, of lichenoid dermatitis with focal interface activity. Involvement of hair follicles and other adnexal structures is shown. c Immunofluorescence shows immunoglobulin G deposition along the epidermal basement membrane. (GIF 312 kb)
Supplemental Figure 2
Electron microscopic studies on patient 2. a First biopsy showed practically no electron-dense deposits, open capillary loops and no extracapillary proliferation. However, the glomerular basement membrane was thickened and lamellated (arrow), which, given the clinical circumstances, was consistent with reparative changes related to previous electron-dense deposits. b Biopsy 3 years later shows electron-dense deposits (arrows). (GIF 230 kb)
Supplemental Figure 3
Electron microscopic study on patient 3. Typical picture of membranous glomerulopathy with subepithelial electron dense deposits (arrows). (GIF 148 kb)
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Sheikine, Y., Woda, C.B., Lee, P.Y. et al. Renal involvement in the immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) disorder. Pediatr Nephrol 30, 1197–1202 (2015). https://doi.org/10.1007/s00467-015-3102-x
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DOI: https://doi.org/10.1007/s00467-015-3102-x