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Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study

Lookup NU author(s): Dr Zohreh Nademi, Professor Mary Slatter, Professor Andrew GenneryORCiD

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Abstract

© 2017 The Authors. Background: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.

Publication metadata

Author(s): Barzaghi F, Amaya Hernandez LC, Neven B, Ricci S, Kucuk ZY, Bleesing JJ, Nademi Z, Slatter MA, Ulloa ER, Shcherbina A, Roppelt A, Worth A, Silva J, Aiuti A, Murguia-Favela L, Speckmann C, Carneiro-Sampaio M, Fernandes JF, Baris S, Ozen A, Karakoc-Aydiner E, Kiykim A, Schulz A, Steinmann S, Notarangelo LD, Gambineri E, Lionetti P, Shearer WT, Forbes LR, Martinez C, Moshous D, Blanche S, Fisher A, Ruemmele FM, Tissandier C, Ouachee-Chardin M, Rieux-Laucat F, Cavazzana M, Qasim W, Lucarelli B, Albert MH, Kobayashi I, Alonso L, Diaz De Heredia C, Kanegane H, Lawitschka A, Seo JJ, Gonzalez-Vicent M, Diaz MA, Goyal RK, Sauer MG, Yesilipek A, Kim M, Yilmaz-Demirdag Y, Bhatia M, Khlevner J, Richmond Padilla EJ, Martino S, Montin D, Neth O, Molinos-Quintana A, Valverde-Fernandez J, Broides A, Pinsk V, Ballauf A, Haerynck F, Bordon V, Dhooge C, Garcia-Lloret ML, Bredius RG, Kalwak K, Haddad E, Seidel MG, Duckers G, Pai S-Y, Dvorak CC, Ehl S, Locatelli F, Goldman F, Gennery AR, Cowan MJ, Roncarolo M-G, Bacchetta R

Publication type: Article

Publication status: Published

Journal: Journal of Allergy and Clinical Immunology

Year: 2018

Volume: 141

Issue: 3

Pages: 1036-1049.e5

Print publication date: 01/03/2018

Online publication date: 11/12/2017

Acceptance date: 12/10/2017

ISSN (print): 0091-6749

ISSN (electronic): 1097-6825

Publisher: Mosby Inc.

URL: https://doi.org/10.1016/j.jaci.2017.10.041

DOI: 10.1016/j.jaci.2017.10.041

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