Portal de Periódicos da CAPES

Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

2023; Elsevier BV; Volume: 152; Issue: 4 Linguagem: Inglês

10.1016/j.jaci.2023.06.015

1097-6825

Maria Elena Maccari, Martin Wolkewitz, Charlotte Schwab, Tiziana Lorenzini, Jennifer W. Leiding, Nathalie Aladjdi, Hassan Abolhassani, Wadih Abou‐Chahla, Alessandro Aiuti, Saba Azarnoush, Safa Barış, Vincent Barlogis, Federica Barzaghi, Ulrich Baumann, Markéta Bloomfield, Nadezda Bohynikova, Damien Bodet, David Boutboul, Giorgia Bucciol, Matthew Buckland, Siobhan O. Burns, Caterina Cancrini, P. Cathébras, Marina Cavazzana, Morgane Cheminant, Matteo Chinello, Peter Čižnár, Tanya Coulter, Maud D’Aveni, Olov Ekwall, Želimir Erić, Efrem Eren, Anders Fasth, Pierre Frange, Benjamin Fournier, Marina Garcia‐Prat, Martine Gardembas, Christoph B. Geier, Sujal Ghosh, Vera Goda, Lennart Hammarström, Fabian Hauck, Maximilian Heeg, Edyta Heropolitańska–Pliszka, Anna Hilfanova, Stephen Jolles, Elif Karakoç-Aydıner, Gerhard Kindle, Ayça Kıykım, Christian Klemann, Patra Koletsi, Sylwia Kołtan, Irina Kondratenko, Julia Körholz, Renate Krüger, Éric Jeziorski, Romain Lévy, G. Le Guenno, Guillaume Lefèvre, Vassilios Lougaris, Antonio Marzollo, Nizar Mahlaoui, Marion Malphettes, Andrea Meinhardt, Étienne Merlin, Isabelle Meyts, Tomáš Milota, Fernando Moreira, Despina Moshous, Anna Mukhinа, Olaf Neth, Jennifer Neubert, Bénédicte Neven, Alexandra Nieters, R. Nové-Josserand, Éric Oksenhendler, Ahmet Özen, Peter Olbrich, Antoinette Perlat, Małgorzata Pac, Jana Pachlopnik Schmid, Lucia Pacillo, Alba Parra-Martínez, Olga Paschenko, Isabelle Pellier, Asena Pınar Sefer, Alessandro Plebani, Dominique Plantaz, Seraina Prader, L. Raffray, Henrike Ritterbusch, Jacques G. Rivière, Beatrice Rivalta, Stephan Rusch, Inga Sakovich, Sinisa Savic, Raphael Scheible, N. Schleinitz, Catharina Schuetz, Ansgar Schulz, Anna Šedivá, Michaëla Semeraro, Svetlana O. Sharapova, Anna Shcherbina, Mary Slatter, Georgios Sogkas, Pere Soler‐Palacín, Carsten Speckmann, Jean-Louis Stéphan, Felipe Suárez, Alberto Tommasini, Johannes Trück, Annette Uhlmann, Koen van Aerde, Joris van Montfrans, Horst von Bernuth, Klaus Warnatz, Tony Williams, Austen Worth, Winnie Ip, Capucine Pïcard, Émilie Catherinot, Zohreh Nademi, Bodo Grimbacher, Lisa Forbes Satter, Sven Kracker, Anita Chandra, Alison M. Condliffe, Stephan Ehl, Markus G. Seidel, Mikko Seppänen, Andrew R. Gennery, Maria Kanariou, Sofia Tantou, Sofia Grigoriadou, Gabriella Cericola, Leif G. Hanitsch, Carmen Scheibenbogen, Eva Hlaváčková, Gergely Kriván, Frances K. McGuire, Timothy Ronan Leahy, David Edgar, Shahrzad Bakhtiar, Peter Bader, Géraldine Blanchard-Rohner, Filomeen Haerynck, Karlien Claes, Kai Lehmberg, Ingo Müller, Susan Farmand, Maria Faßhauer, Dagmar Graf, João Farela Neves, Larysa Kostyuchenko, Luis Ignacio González‐Granado, Miloš Jeseňák, Maria Carrabba, Fabio Gavarini, Claudio Pignata, Giuliana Giardino, Ilknur Kökçü Karadağ, Alişan Yıldıran, Gonca Hancıoğlu, Pavlína Králíčková, Sandra Steinmann, Barbara Pietrucha, Michael Gernert, Maarja Soomann, Torsten Witte, Adam Markocsy, Beata Wolska‐Kuśnierz, Philippe Randrianomenjanahary, Jérémie Rouger, Stavroula Kostaridou, Dariia V. Osypchuk, Yulia Rodina, О. А. Швец,

Platelet Disorders and Treatments

Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS.APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.