ESPN 54th Annual Meeting

ESPN 2022


 
Kidney and Bone Marrow Involvement in IPEX Syndrome with Atypical Presentation: the “Fil Rouge” of Treg between IPEX Features and other Clinical Entities?
EDOARDO LA PORTA 1 MICAELA GENTILE 1 ANDREA ANGELETTI 1 GIANMARCO GHIGGERI 1 GIANLUCA CARIDI 1 FRANCESCA LUGANI 1 LORENZO NESCIS 1 ENRICO FIACCADORI 2 ALBERTO MAGNASCO 1 ANTONELLA TRIVELLI 1 ENRICO VERRINA 1

1- NEPHROLOGY, DIALYSIS AND TRANSPLANTATION, IRCCS GASLINI HOSPITAL, GENOA, ITALY
2- DIPARTIMENTO DI MEDICINA E CHIRURGIA, UNIVERSITà DI PARMA, PARMA, ITALY
 
Introduction:

The transcription factor Forkhead box protein P3 (FOXP3) is central to the function of regulatory T cells (Treg). Mutations in the FOXP3 gene lead to a systemic disease called immune dysregulation, polyendocrinopathy and enteropathy, X-linked syndrome (IPEX). Some FOXP3 mutations were associated with atypical presentation including rare disease

Material and methods:

We reported two cases of IPEX characterized by kidney and hematologic involvement

Results:

Patient 1. A 16-year male with a clinical diagnosis of ALPS treated with sirolimus. Due to the onset of proteinuria and decreased kidney function, a kidney biopsy was performed, with diagnosis of membranous glomerulopathy (MGP). PLA2R on serum and tissues were negative. A mutation of the FOXP3 gene c.779T>A (p.L260Q), never reported before and predicted to be Likely Pathogenic was found. The patient does not present the classical triad of IPEX, and Treg resulted normal. He was treated with steroids and continues sirolimus with good control of proteinuria and stable kidney function.

Patient 2. A 2-year child was diagnosed with a bone marrow failure, genetic investigations were negative. He presented elevated serum IgG4 and kidney failure. A kidney biopsy showed MGP associated with TIN. IF and IHC for PLA2R resulted positive. IHC for IgG4 resulted positive. After the diagnosis of IgG4 RD, steroid therapy was started, without clinical response. Thereafter the patient underwent bone marrow transplant from his brother (HLA-identical). We performed a new genetic exam. A hemizygous mutation of the FOXP3 gene c.1087A>G (p.I363V), already described in the literature, was found, also in the mother and in the proband’s brother, thus a diagnosis of IPEX was done. Therefore, Treg resulted normal for brother and mother but not in our patient. The patient underwent kidney transplantation, and after one year he presents normal kidney function.

 

Conclusions:

MGP pathogenesis in IPEX is consistent with recent evidence of unbalance of Th17/Treg in idiopathic MGP, with significant reduction of Treg cell and FOXP3 expression. IPEX poses a diagnostic challenge considering the spectrum of different phenotypes, but to recognize kidney involvement, together with the growing use of wide genomic analysis, could play a central role.