Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity
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Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity. / Maccari, Maria Elena; Wolkewitz, Martin; Schwab, Charlotte; Lorenzini, Tiziana; Leiding, Jennifer W; Aladjdi, Nathalie; Abolhassani, Hassan; Abou-Chahla, Wadih; Aiuti, Alessandro; Azarnoush, Saba; Baris, Safa; Barlogis, Vincent; Barzaghi, Federica; Baumann, Ulrich; Bloomfield, Marketa; Bohynikova, Nadezda; Bodet, Damien; Boutboul, David; Bucciol, Giorgia; Buckland, Matthew S; Burns, Siobhan O; Cancrini, Caterina; Cathébras, Pascal; Cavazzana, Marina; Cheminant, Morgane; Chinello, Matteo; Ciznar, Peter; Coulter, Tanya I; D'Aveni, Maud; Ekwall, Olov; Eric, Zelimir; Eren, Efrem; Fasth, Anders; Frange, Pierre; Fournier, Benjamin; Garcia-Prat, Marina; Gardembas, Martine; Geier, Christoph; Ghosh, Sujal; Goda, Vera; Hammarström, Lennart; Hauck, Fabian; Heeg, Maximilian; Heropolitanska-Pliszka, Edyta; Hilfanova, Anna; Jolles, Stephen; Karakoc-Aydiner, Elif; Kindle, Gerhard R; Kiykim, Ayca; Klemann, Christian; Koletsi, Patra; Koltan, Sylwia; Kondratenko, Irina; Körholz, Julia; Krüger, Renate; Jeziorski, Eric; Levy, Romain; Le Guenno, Guillaume; Lefevre, Guillaume; Lougaris, Vassilios; Marzollo, Antonio; Mahlaoui, Nizar; Malphettes, Marion; Meinhardt, Andrea; Merlin, Etienne; Meyts, Isabelle; Milota, Tomas; Moreira, Fernando; Moshous, Despina; Mukhina, Anna; Neth, Olaf; Neubert, Jennifer; Neven, Benedicte; Nieters, Alexandra; Nove-Josserand, Raphaele; Oksenhendler, Eric; Ozen, Ahmet; Olbrich, Peter; Perlat, Antoinette; Pac, Malgorzata; Schmid, Jana Pachlopnik; Pacillo, Lucia; Parra-Martinez, Alba; Paschenko, Olga; Pellier, Isabelle; Sefer, Asena Pinar; Plebani, Alessandro; Plantaz, Dominique; Prader, Seraina; Raffray, Loic; Ritterbusch, Henrike; Riviere, Jacques G; Rivalta, Beatrice; Rusch, Stephan; Sakovich, Inga; Savic, Sinisa; Scheible, Raphael; Schleinitz, Nicolas; Schuetz, Catharina; Schulz, Ansgar; Sediva, Anna; Semeraro, Michaela; Sharapova, Svetlana O; Shcherbina, Anna; Slatter, Mary A; Sogkas, Georgios; Soler-Palacin, Pere; Speckmann, Carsten; Stephan, Jean-Louis; Suarez, Felipe; Tommasini, Alberto; Trück, Johannes; Uhlmann, Annette; van Aerde, Koen J; van Montfrans, Joris; von Bernuth, Horst; Warnatz, Klaus; Williams, Tony; Worth, Austen J J; Ip, Winnie; Picard, Capucine; Catherinot, Emilie; Nademi, Zohreh; Grimbacher, Bodo; Forbes Satter, Lisa R; Kracker, Sven; Chandra, Anita; Condliffe, Alison M; Ehl, Stephan; European Society for Immunodeficiencies Registry Working Party.
in: J ALLERGY CLIN IMMUN, Jahrgang 152, Nr. 4, 10.2023, S. 984-996.e10.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity
AU - Maccari, Maria Elena
AU - Wolkewitz, Martin
AU - Schwab, Charlotte
AU - Lorenzini, Tiziana
AU - Leiding, Jennifer W
AU - Aladjdi, Nathalie
AU - Abolhassani, Hassan
AU - Abou-Chahla, Wadih
AU - Aiuti, Alessandro
AU - Azarnoush, Saba
AU - Baris, Safa
AU - Barlogis, Vincent
AU - Barzaghi, Federica
AU - Baumann, Ulrich
AU - Bloomfield, Marketa
AU - Bohynikova, Nadezda
AU - Bodet, Damien
AU - Boutboul, David
AU - Bucciol, Giorgia
AU - Buckland, Matthew S
AU - Burns, Siobhan O
AU - Cancrini, Caterina
AU - Cathébras, Pascal
AU - Cavazzana, Marina
AU - Cheminant, Morgane
AU - Chinello, Matteo
AU - Ciznar, Peter
AU - Coulter, Tanya I
AU - D'Aveni, Maud
AU - Ekwall, Olov
AU - Eric, Zelimir
AU - Eren, Efrem
AU - Fasth, Anders
AU - Frange, Pierre
AU - Fournier, Benjamin
AU - Garcia-Prat, Marina
AU - Gardembas, Martine
AU - Geier, Christoph
AU - Ghosh, Sujal
AU - Goda, Vera
AU - Hammarström, Lennart
AU - Hauck, Fabian
AU - Heeg, Maximilian
AU - Heropolitanska-Pliszka, Edyta
AU - Hilfanova, Anna
AU - Jolles, Stephen
AU - Karakoc-Aydiner, Elif
AU - Kindle, Gerhard R
AU - Kiykim, Ayca
AU - Klemann, Christian
AU - Koletsi, Patra
AU - Koltan, Sylwia
AU - Kondratenko, Irina
AU - Körholz, Julia
AU - Krüger, Renate
AU - Jeziorski, Eric
AU - Levy, Romain
AU - Le Guenno, Guillaume
AU - Lefevre, Guillaume
AU - Lougaris, Vassilios
AU - Marzollo, Antonio
AU - Mahlaoui, Nizar
AU - Malphettes, Marion
AU - Meinhardt, Andrea
AU - Merlin, Etienne
AU - Meyts, Isabelle
AU - Milota, Tomas
AU - Moreira, Fernando
AU - Moshous, Despina
AU - Mukhina, Anna
AU - Neth, Olaf
AU - Neubert, Jennifer
AU - Neven, Benedicte
AU - Nieters, Alexandra
AU - Nove-Josserand, Raphaele
AU - Oksenhendler, Eric
AU - Ozen, Ahmet
AU - Olbrich, Peter
AU - Perlat, Antoinette
AU - Pac, Malgorzata
AU - Schmid, Jana Pachlopnik
AU - Pacillo, Lucia
AU - Parra-Martinez, Alba
AU - Paschenko, Olga
AU - Pellier, Isabelle
AU - Sefer, Asena Pinar
AU - Plebani, Alessandro
AU - Plantaz, Dominique
AU - Prader, Seraina
AU - Raffray, Loic
AU - Ritterbusch, Henrike
AU - Riviere, Jacques G
AU - Rivalta, Beatrice
AU - Rusch, Stephan
AU - Sakovich, Inga
AU - Savic, Sinisa
AU - Scheible, Raphael
AU - Schleinitz, Nicolas
AU - Schuetz, Catharina
AU - Schulz, Ansgar
AU - Sediva, Anna
AU - Semeraro, Michaela
AU - Sharapova, Svetlana O
AU - Shcherbina, Anna
AU - Slatter, Mary A
AU - Sogkas, Georgios
AU - Soler-Palacin, Pere
AU - Speckmann, Carsten
AU - Stephan, Jean-Louis
AU - Suarez, Felipe
AU - Tommasini, Alberto
AU - Trück, Johannes
AU - Uhlmann, Annette
AU - van Aerde, Koen J
AU - van Montfrans, Joris
AU - von Bernuth, Horst
AU - Warnatz, Klaus
AU - Williams, Tony
AU - Worth, Austen J J
AU - Ip, Winnie
AU - Picard, Capucine
AU - Catherinot, Emilie
AU - Nademi, Zohreh
AU - Grimbacher, Bodo
AU - Forbes Satter, Lisa R
AU - Kracker, Sven
AU - Chandra, Anita
AU - Condliffe, Alison M
AU - Ehl, Stephan
AU - European Society for Immunodeficiencies Registry Working Party
AU - Farmand, Susan
N1 - Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.
PY - 2023/10
Y1 - 2023/10
N2 - BACKGROUND: 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.OBJECTIVES: 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.METHODS: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.RESULTS: 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.CONCLUSIONS: 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.
AB - BACKGROUND: 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.OBJECTIVES: 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.METHODS: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.RESULTS: 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.CONCLUSIONS: 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.
KW - Humans
KW - Phosphatidylinositol 3-Kinase/genetics
KW - Phosphatidylinositol 3-Kinases/genetics
KW - Class I Phosphatidylinositol 3-Kinases
KW - CTLA-4 Antigen/genetics
KW - Mutation
KW - Primary Immunodeficiency Diseases/genetics
KW - Registries
U2 - 10.1016/j.jaci.2023.06.015
DO - 10.1016/j.jaci.2023.06.015
M3 - SCORING: Journal article
C2 - 37390899
VL - 152
SP - 984-996.e10
JO - J ALLERGY CLIN IMMUN
JF - J ALLERGY CLIN IMMUN
SN - 0091-6749
IS - 4
ER -