Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry
Year: 2018
Type: article
Study design: Observational Study
Abstract: (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2). Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2-3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission), while bowel inflammation (3 complete, 3 partial, 9 no remission) and cytopenia (3 complete, 2 partial, 9 no remission) responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies.
Source: Frontiers in Immunology
Authors: Maria Elena Maccari, Hassan Abolhassani, Asghar Aghamohammadi, Alessandro Aiuti, Olga Aleinikova, Catherine Bangs, Safa Baris, Federica Barzaghi, Helen Baxendale, Matthew Buckland, Siobhan O. Burns, Caterina Cancrini, Andrew Cant, Pascal Cathébras, Marina Cavazzana, Anita Chandra, Francesca Conti, Tanya Coulter, Lisa A. Devlin, J. David M. Edgar, Saul Faust, Alain Fischer, Marina Garcia Prat, Lennart Hammarström, Maximilian Heeg, Stephen Jolles, Elif Karakoc-Aydiner, Gerhard Kindle, Ayca Kiykim, Dinakantha Kumararatne, Bodo Grimbacher, Hilary Longhurst, Nizar Mahlaoui, Tomas Milota, Fernando Moreira, Despina Moshous, Anna Mukhina, Olaf Neth, Benedicte Neven, Alexandra Nieters, Peter Olbrich, Ahmet Ozen, Jana Pachlopnik Schmid, Capucine Picard, Seraina Prader, William Rae, Janine Reichenbach, Stephan Rusch, Sinisa Savic, Alessia Scarselli, Raphael Scheible, Anna Sediva, Svetlana O. Sharapova, Anna Shcherbina, Mary Slatter, Pere Soler-Palacin, Aurelie Stanislas, Felipe Suarez, Francesca Tucci, Annette Uhlmann, Joris van Montfrans, Klaus Warnatz, Anthony Peter Williams, Phil Wood, Sven Kracker, Alison Mary Condliffe, Stephan Ehl
Institutions: University of Freiburg, University Medical Center Freiburg, Karolinska University Hospital, Karolinska Institutet, Children's Medical Center, Tehran University of Medical Sciences, The San Raffaele Telethon Institute for Gene Therapy, Belarusian Research Center For Pediatric Oncology and Hematology, Marmara University, Royal Papworth Hospital, The Royal Free Hospital, University of Rome Tor Vergata, Bambino Gesù Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne Hospital, Centre Hospitalier Universitaire de Saint-Étienne, Hôpital Necker-Enfants Malades, Inserm, Sorbonne Paris Cité, Assistance Publique – Hôpitaux de Paris, Institut des Maladies Génétiques Imagine, Université Paris Descartes, University of Cambridge, Addenbrooke's Hospital, Queen's University Belfast, Royal Victoria Hospital, University Hospital Southampton NHS Foundation Trust, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, University Hospital of Wales, Centre de Référence Déficits Immunitaires Héréditaires, Charles University, University Hospital in Motol, Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío, University of Zurich, University Children's Hospital Zurich, Wilhelmina Children's Hospital, St James's University Hospital, University of Sheffield
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W2792908940