Long-term outcome in Wiskott-Aldrich syndrome and X-linked thrombocytopenia patients: an observational -prospective multi-center study of the Italian Primary Immune Deficiency Network (IPINET)
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Le résumé fourni par la source
Background Wiskott-Aldrich Syndrome (WAS) is characterized by eczema, infections, and severe bleeding, but may also include autoimmunity and malignancy. Subjects with X-linked thrombocytopenia (XLT) can display a mild phenotype, although severe complications may occur at any age. WAS and XLT are caused by mutations of the WAS gene. However, retrospective studies have shown conflicting results about their genotype–phenotype correlation and their relative risk of complications. Methods To evaluate the outcome of patients with WAS or XLT, since January 2004, patients with identified WAS mutations were enrolled in the WAS/XLT IPINet registry at diagnosis and annually evaluated until December 2018 by participating AIEOP-IPINet centers; data were prospectively collected by each participating center throughout a web-based centralized system and then retrieved from the registry for the analysis. This prospective study enrolled 117 patients (according to Zhu criteria, 92 were affected by WAS and 25 by XLT) with appropriate hematological features and documented WAS mutation. Findings The median follow-up was 6 years (range 1–30 years), resulting in 1110 patient years. At diagnosis, only the patients with WAS presented invasive infections, such as sepsis, meningitis, cerebral abscesses, herpetic infections, and candida infections, while patients with XLT did not present invasive infections. The most common autoimmune manifestations in patients with WAS were hemolytic anemia (20%) and vasculitis (9.3%), inflammatory bowel disease (5%), arthritis (4%), nephropathy (2%), and coeliac disease (1%). Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) was performed in 71 (61%), autologous hematopoietic stem cell gene therapy (HSC-GT) in 10 (8.5%), splenectomy in 16 (14%) patients, while 26 patients (22%) received none of these therapies. The overall survival at 25-year follow-up was 75% for patients with WAS after HSCT. Considering the cut-off date year 2000, it improved to >80%. Patients with WAS treated by haploidentical HSCT with αβTCRT-/CD19 B-cell depletion or gene therapy showed 100% survival at 5 years. The overall survival rate at the 20-year follow-up of the 25 patients with XLT was 83% but with a cumulative incidence of 100% and 19% of infections and autoimmunity, respectively, at the 15-year follow-up. Interpretation The evidence of the heterogeneity of WAS and XLT outcomes could be instrumental to draw updated recommendations for the management of the patients affected by these rare conditions. It would be desirable to expand the tools to estimate the risk of infectious and autoimmune events in patients with XLT and the impact of their treatment, including HSCT over time. Funding This study was funded by the European Union–Next Generation EU–NRRP M6C2–Investment 2.1 Enhancement and strengthening of biomedical research in the NHS, Ministero della Salute (PNRR-MR1-2022-12376594). A.S., A.A., P.C., F.F., C.M.P., C.F., D.L., G.S., M.D., M.C., P.A., B.A., P.F. are part of the European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN-RITA, project 739543).
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Long-term outcome in Wiskott-Aldrich syndrome and X-linked thrombocytopenia patients: an observational -prospective multi-center study of the Italian Primary Immune Deficiency Network (IPINET)
- Date Crossref
- 01/06/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia pays non établi dans la noticeÉtablissement de santé
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University of Brescia Unit of Pediatric Immunology pays non établi dans la noticeUniversité ou école supérieure
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Azienda USL di Bologna pays non établi dans la noticeÉtablissement de santé
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University of Bologna Department of Medical and Surgical Sciences pays non établi dans la noticeUniversité ou école supérieure
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National Institute of Allergy and Infectious Diseases pays non établi dans la noticeStructure de recherche
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Bambino Gesù Children's Hospital pays non établi dans la noticeÉtablissement de santé
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Istituti di Ricovero e Cura a Carattere Scientifico pays non établi dans la noticeÉtablissement de santé
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Vita-Salute San Raffaele University pays non établi dans la noticeUniversité ou école supérieure
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The San Raffaele Telethon Institute for Gene Therapy pays non établi dans la noticeStructure de recherche
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Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele pays non établi dans la noticeÉtablissement de santé
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University of Padua pays non établi dans la noticeUniversité ou école supérieure
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IRCCS Materno Infantile Burlo Garofolo pays non établi dans la noticeÉtablissement de santé
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Unit of Pediatric Immunology — University of Brescia et Azienda USL di Bologna, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.