Research ExplorerPublicationsActivated phosphoinositide 3-kinase δ syndrome: Update from ...

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

Standard

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, Vol. 152, No. 4, 10.2023, p. 984-996.e10.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Maccari, ME, Wolkewitz, M, Schwab, C, Lorenzini, T, Leiding, JW, Aladjdi, N, Abolhassani, H, Abou-Chahla, W, Aiuti, A, Azarnoush, S, Baris, S, Barlogis, V, Barzaghi, F, Baumann, U, Bloomfield, M, Bohynikova, N, Bodet, D, Boutboul, D, Bucciol, G, Buckland, MS, Burns, SO, Cancrini, C, Cathébras, P, Cavazzana, M, Cheminant, M, Chinello, M, Ciznar, P, Coulter, TI, D'Aveni, M, Ekwall, O, Eric, Z, Eren, E, Fasth, A, Frange, P, Fournier, B, Garcia-Prat, M, Gardembas, M, Geier, C, Ghosh, S, Goda, V, Hammarström, L, Hauck, F, Heeg, M, Heropolitanska-Pliszka, E, Hilfanova, A, Jolles, S, Karakoc-Aydiner, E, Kindle, GR, Kiykim, A, Klemann, C, Koletsi, P, Koltan, S, Kondratenko, I, Körholz, J, Krüger, R, Jeziorski, E, Levy, R, Le Guenno, G, Lefevre, G, Lougaris, V, Marzollo, A, Mahlaoui, N, Malphettes, M, Meinhardt, A, Merlin, E, Meyts, I, Milota, T, Moreira, F, Moshous, D, Mukhina, A, Neth, O, Neubert, J, Neven, B, Nieters, A, Nove-Josserand, R, Oksenhendler, E, Ozen, A, Olbrich, P, Perlat, A, Pac, M, Schmid, JP, Pacillo, L, Parra-Martinez, A, Paschenko, O, Pellier, I, Sefer, AP, Plebani, A, Plantaz, D, Prader, S, Raffray, L, Ritterbusch, H, Riviere, JG, Rivalta, B, Rusch, S, Sakovich, I, Savic, S, Scheible, R, Schleinitz, N, Schuetz, C, Schulz, A, Sediva, A, Semeraro, M, Sharapova, SO, Shcherbina, A, Slatter, MA, Sogkas, G, Soler-Palacin, P, Speckmann, C, Stephan, J-L, Suarez, F, Tommasini, A, Trück, J, Uhlmann, A, van Aerde, KJ, van Montfrans, J, von Bernuth, H, Warnatz, K, Williams, T, Worth, AJJ, Ip, W, Picard, C, Catherinot, E, Nademi, Z, Grimbacher, B, Forbes Satter, LR, Kracker, S, Chandra, A, Condliffe, AM, Ehl, S & European Society for Immunodeficiencies Registry Working Party 2023, 'Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity', J ALLERGY CLIN IMMUN, vol. 152, no. 4, pp. 984-996.e10. https://doi.org/10.1016/j.jaci.2023.06.015

APA

Maccari, M. E., Wolkewitz, M., Schwab, C., Lorenzini, T., Leiding, J. W., Aladjdi, N., Abolhassani, H., Abou-Chahla, W., Aiuti, A., Azarnoush, S., Baris, S., Barlogis, V., Barzaghi, F., Baumann, U., Bloomfield, M., Bohynikova, N., Bodet, D., Boutboul, D., Bucciol, G., ... European Society for Immunodeficiencies Registry Working Party (2023). Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity. J ALLERGY CLIN IMMUN, 152(4), 984-996.e10. https://doi.org/10.1016/j.jaci.2023.06.015

Vancouver

Maccari ME, Wolkewitz M, Schwab C, Lorenzini T, Leiding JW, Aladjdi N et al. Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity. J ALLERGY CLIN IMMUN. 2023 Oct;152(4):984-996.e10. https://doi.org/10.1016/j.jaci.2023.06.015

Bibtex

@article{5ffbbab2d0ed4c7eb1b532cced35d4fb,
title = "Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity",
abstract = "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.",
keywords = "Humans, Phosphatidylinositol 3-Kinase/genetics, Phosphatidylinositol 3-Kinases/genetics, Class I Phosphatidylinositol 3-Kinases, CTLA-4 Antigen/genetics, Mutation, Primary Immunodeficiency Diseases/genetics, Registries",
author = "Maccari, {Maria Elena} and Martin Wolkewitz and Charlotte Schwab and Tiziana Lorenzini and Leiding, {Jennifer W} and Nathalie Aladjdi and Hassan Abolhassani and Wadih Abou-Chahla and Alessandro Aiuti and Saba Azarnoush and Safa Baris and Vincent Barlogis and Federica Barzaghi and Ulrich Baumann and Marketa Bloomfield and Nadezda Bohynikova and Damien Bodet and David Boutboul and Giorgia Bucciol and Buckland, {Matthew S} and Burns, {Siobhan O} and Caterina Cancrini and Pascal Cath{\'e}bras and Marina Cavazzana and Morgane Cheminant and Matteo Chinello and Peter Ciznar and Coulter, {Tanya I} and Maud D'Aveni and Olov Ekwall and Zelimir Eric and Efrem Eren and Anders Fasth and Pierre Frange and Benjamin Fournier and Marina Garcia-Prat and Martine Gardembas and Christoph Geier and Sujal Ghosh and Vera Goda and Lennart Hammarstr{\"o}m and Fabian Hauck and Maximilian Heeg and Edyta Heropolitanska-Pliszka and Anna Hilfanova and Stephen Jolles and Elif Karakoc-Aydiner and Kindle, {Gerhard R} and Ayca Kiykim and Christian Klemann and Patra Koletsi and Sylwia Koltan and Irina Kondratenko and Julia K{\"o}rholz and Renate Kr{\"u}ger and Eric Jeziorski and Romain Levy and {Le Guenno}, Guillaume and Guillaume Lefevre and Vassilios Lougaris and Antonio Marzollo and Nizar Mahlaoui and Marion Malphettes and Andrea Meinhardt and Etienne Merlin and Isabelle Meyts and Tomas Milota and Fernando Moreira and Despina Moshous and Anna Mukhina and Olaf Neth and Jennifer Neubert and Benedicte Neven and Alexandra Nieters and Raphaele Nove-Josserand and Eric Oksenhendler and Ahmet Ozen and Peter Olbrich and Antoinette Perlat and Malgorzata Pac and Schmid, {Jana Pachlopnik} and Lucia Pacillo and Alba Parra-Martinez and Olga Paschenko and Isabelle Pellier and Sefer, {Asena Pinar} and Alessandro Plebani and Dominique Plantaz and Seraina Prader and Loic Raffray and Henrike Ritterbusch and Riviere, {Jacques G} and Beatrice Rivalta and Stephan Rusch and Inga Sakovich and Sinisa Savic and Raphael Scheible and Nicolas Schleinitz and Catharina Schuetz and Ansgar Schulz and Anna Sediva and Michaela Semeraro and Sharapova, {Svetlana O} and Anna Shcherbina and Slatter, {Mary A} and Georgios Sogkas and Pere Soler-Palacin and Carsten Speckmann and Jean-Louis Stephan and Felipe Suarez and Alberto Tommasini and Johannes Tr{\"u}ck and Annette Uhlmann and {van Aerde}, {Koen J} and {van Montfrans}, Joris and {von Bernuth}, Horst and Klaus Warnatz and Tony Williams and Worth, {Austen J J} and Winnie Ip and Capucine Picard and Emilie Catherinot and Zohreh Nademi and Bodo Grimbacher and {Forbes Satter}, {Lisa R} and Sven Kracker and Anita Chandra and Condliffe, {Alison M} and Stephan Ehl and {European Society for Immunodeficiencies Registry Working Party} and Susan Farmand",
note = "Copyright {\textcopyright} 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.",
year = "2023",
month = oct,
doi = "10.1016/j.jaci.2023.06.015",
language = "English",
volume = "152",
pages = "984--996.e10",
journal = "J ALLERGY CLIN IMMUN",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "4",

}

RIS

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 -