Natural history of clinical manifestations in activated phosphoinositide 3-kinase δ syndrome (APDS): Time-to-event analyses using the European Society for Immunodeficiencies-APDS registry
Year: 2025
Type: article
Study design: Observational Study
Abstract: Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive disease characterised by immunodeficiency, immune dysregulation, and risk of malignancies. To further characterise the natural history of APDS, we analysed patient characteristics, manifestations, treatment use, and combinations of manifestations and combinations of treatments over time using longitudinal data from registration and follow-up visits in the European Society for Immunodeficiencies (ESID)-APDS registry. 140 patients were included (mean age: 17.7 years at registration; 19.1 years at last follow-up). Manifestation burden was high from childhood (patients experienced up to 9 manifestations by age 10). The number of treatments increased with age, with a 64 % probability of receiving ≥1 by age 10. Life-threatening APDS complications led to 13 deaths reported over 2.6 years' mean follow-up. These data highlight the chronic, progressive nature of APDS and its long-term impact on patients, with a high manifestation load and early mortality, despite widespread symptomatic treatment use.
Source: Clinical Immunology
Authors: Maria Elena Maccari, Sven Kracker, Anita Chandra, Stephan Ehl, Markus G. Seidel, Joanne Tutein Nolthenius, Laura J. Clark, Jennifer Page, Annabel Griffiths, John Whalen, Abolhassani Hassan, Alachkar Hana, Aladjidi Nathalie, Arkwright Peter, Azarnoush Saba, Baris Safa, Barlogis Vincent, Bastard Paul, Baumann Ulrich, Bernatoniene Jolanta, Blanchard-Rohner Geraldine, Bloomfield Markéta, Boz Valentina, Bucciol Giorgia, Buckland Matthew, Cancrini Caterina, Cant Andrew, Castelle Martin, Cavazzana Marina, Chinello Matteo, Condliffe Alison, Dion Jérémie, Ekwall Olov, Farmaki Evangelia, Fasshauer Maria, Fischer Marco, Frange Pierre, Galicier Lionel, Garcia Prat Marina, Gennery Andrew, Ghosh Sujal, Gkantaras Antonios, Goda Vera, Grigoriadou Sofia, Grimbacher Bodo, Hauck Fabian, Heropolitańska-Pliszka Edyta, Kindle Gerhard, Kiykim Ayça, Klemann Christian, Koerholz Julia, Koletsi Patra, Kołtan Sylwia, Lodi Lorenzo, Lougaris Vassilios, Mahlaoui Nizar, Malphettes Marion, Marzollo Antonio, Milota Tomas, Nademi Zohreh, Olbrich Peter, Ozen Ahmed, Pachlopnik Schmid Jana, Patel Smita, Perlat Antoinette, Plebani Alessandro, Prader Seraina, Rivalta, G. Rivière Jacques, Schleinitz Nicolas, Schulz Ansgar, S. Kilic Sara, Sediva Anna, Semeraro Michaela, Shillitoe Benjamin, Slatter Mary, Sogkas Georgios, Soler Palacin Pere, Soomann Maarja, Stadon Catherine, Suarez Felipe, Trück Johannes, Uhlmann Annette, Worth Austen, Yucel Esra, Zelimir Eric
Institutions: University of Freiburg, University Medical Center Freiburg, Inserm, Université Paris Cité, Institut des Maladies Génétiques Imagine, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust, Medical University of Graz, Pharming Group (Netherlands), Costello Medical Consulting (United Kingdom)
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,400
OpenAlex ID: W4415747970