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
Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions abo...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/180501 |
| Acceso en línea: | http://hdl.handle.net/10261/180501 |
| Access Level: | acceso abierto |
| Palabra clave: | Activated phosphoinositide 3-kinase δ syndrome PIK3CD PIK3R1 Registry Natural history Rapamycin |
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Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome RegistryMaccari, María ElenaAbolhassani, HassanAghamohammadi, AsgharAiuti, AlessandroAleinikova, OlgaBangs, CatherineBaris, SafaBarzaghi, FedericaBaxendale, HelenBuckland, MatthewBurns, Siobhan O.Cancrini, CaterinaCant, AndrewCathébras, PascalCavazzana, MarinaChandra, AnitaConti, FrancescaCoulter, TanyaDevlin, Lisa A.Edgar, J. David M.Faust, SaulFischer, AlainGarcía Prat, MarinaHammarström, LennartHeeg, MaximilianJolles, StephenKarakoc-Aydiner, ElifKindle, GerhardKiykim, AycaKumararatne, DinakanthaGrimbacher, BodoLonghurst, HilaryMahlaoui, NizarMilota, TomasMoreira, FernandoMoshous, DespinaMukhina, AnnaNeth, OlafNeven, BenedicteNieters, AlexandraOlbrich, PeterOzen, AhmetPachlopnik Schmid, JanaPicard, CapucinePrader, SerainaRae, WilliamReichenbach, JanineRusch, StephanSavic, SinisaScarselli, AlessiaScheible, RaphaelSediva, AnnaSharapova, Svetlana O.Shcherbina, AnnaSlatter, MarySoler-Palacín, PereStanislas, AurelieSuárez, FelipeTucci, FrancescaUhlmann, Annevan Montfrans, JorisWarnatz, KlausWilliams, Anthony PeterWood, PhilKracker, SvenCondliffe, Alison MaryEhl, StephanActivated phosphoinositide 3-kinase δ syndromePIK3CDPIK3R1RegistryNatural historyRapamycinActivated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (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.This study was supported by the German Federal Ministry of Education and Research (BMBF 01E01303). The ESID-APDS registry is supported by the pharmaceutical companies Novartis, GlaxoSmithKline, and UCB UK.Peer reviewedFrontiers MediaFederal Ministry of Education and Research (Germany)NovartisGlaxoSmithKlineConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/180501reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3389/fimmu.2018.00543Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1805012026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
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 |
| title |
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 |
| spellingShingle |
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 Maccari, María Elena Activated phosphoinositide 3-kinase δ syndrome PIK3CD PIK3R1 Registry Natural history Rapamycin |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| dc.creator.none.fl_str_mv |
Maccari, María Elena Abolhassani, Hassan Aghamohammadi, Asghar Aiuti, Alessandro Aleinikova, Olga Bangs, Catherine Baris, Safa Barzaghi, Federica Baxendale, Helen Buckland, Matthew Burns, Siobhan O. Cancrini, Caterina Cant, Andrew Cathébras, Pascal Cavazzana, Marina Chandra, Anita Conti, Francesca Coulter, Tanya Devlin, Lisa A. Edgar, J. David M. Faust, Saul Fischer, Alain García Prat, Marina Hammarström, Lennart Heeg, Maximilian Jolles, Stephen Karakoc-Aydiner, Elif Kindle, Gerhard Kiykim, Ayca Kumararatne, Dinakantha Grimbacher, Bodo Longhurst, Hilary Mahlaoui, Nizar Milota, Tomas Moreira, Fernando Moshous, Despina Mukhina, Anna Neth, Olaf Neven, Benedicte Nieters, Alexandra Olbrich, Peter Ozen, Ahmet Pachlopnik Schmid, Jana Picard, Capucine Prader, Seraina Rae, William Reichenbach, Janine Rusch, Stephan Savic, Sinisa Scarselli, Alessia Scheible, Raphael Sediva, Anna Sharapova, Svetlana O. Shcherbina, Anna Slatter, Mary Soler-Palacín, Pere Stanislas, Aurelie Suárez, Felipe Tucci, Francesca Uhlmann, Anne van Montfrans, Joris Warnatz, Klaus Williams, Anthony Peter Wood, Phil Kracker, Sven Condliffe, Alison Mary Ehl, Stephan |
| author |
Maccari, María Elena |
| author_facet |
Maccari, María Elena Abolhassani, Hassan Aghamohammadi, Asghar Aiuti, Alessandro Aleinikova, Olga Bangs, Catherine Baris, Safa Barzaghi, Federica Baxendale, Helen Buckland, Matthew Burns, Siobhan O. Cancrini, Caterina Cant, Andrew Cathébras, Pascal Cavazzana, Marina Chandra, Anita Conti, Francesca Coulter, Tanya Devlin, Lisa A. Edgar, J. David M. Faust, Saul Fischer, Alain García Prat, Marina Hammarström, Lennart Heeg, Maximilian Jolles, Stephen Karakoc-Aydiner, Elif Kindle, Gerhard Kiykim, Ayca Kumararatne, Dinakantha Grimbacher, Bodo Longhurst, Hilary Mahlaoui, Nizar Milota, Tomas Moreira, Fernando Moshous, Despina Mukhina, Anna Neth, Olaf Neven, Benedicte Nieters, Alexandra Olbrich, Peter Ozen, Ahmet Pachlopnik Schmid, Jana Picard, Capucine Prader, Seraina Rae, William Reichenbach, Janine Rusch, Stephan Savic, Sinisa Scarselli, Alessia Scheible, Raphael Sediva, Anna Sharapova, Svetlana O. Shcherbina, Anna Slatter, Mary Soler-Palacín, Pere Stanislas, Aurelie Suárez, Felipe Tucci, Francesca Uhlmann, Anne van Montfrans, Joris Warnatz, Klaus Williams, Anthony Peter Wood, Phil Kracker, Sven Condliffe, Alison Mary Ehl, Stephan |
| author_role |
author |
| author2 |
Abolhassani, Hassan Aghamohammadi, Asghar Aiuti, Alessandro Aleinikova, Olga Bangs, Catherine Baris, Safa Barzaghi, Federica Baxendale, Helen Buckland, Matthew Burns, Siobhan O. Cancrini, Caterina Cant, Andrew Cathébras, Pascal Cavazzana, Marina Chandra, Anita Conti, Francesca Coulter, Tanya Devlin, Lisa A. Edgar, J. David M. Faust, Saul Fischer, Alain García Prat, Marina Hammarström, Lennart Heeg, Maximilian Jolles, Stephen Karakoc-Aydiner, Elif Kindle, Gerhard Kiykim, Ayca Kumararatne, Dinakantha Grimbacher, Bodo Longhurst, Hilary Mahlaoui, Nizar Milota, Tomas Moreira, Fernando Moshous, Despina Mukhina, Anna Neth, Olaf Neven, Benedicte Nieters, Alexandra Olbrich, Peter Ozen, Ahmet Pachlopnik Schmid, Jana Picard, Capucine Prader, Seraina Rae, William Reichenbach, Janine Rusch, Stephan Savic, Sinisa Scarselli, Alessia Scheible, Raphael Sediva, Anna Sharapova, Svetlana O. Shcherbina, Anna Slatter, Mary Soler-Palacín, Pere Stanislas, Aurelie Suárez, Felipe Tucci, Francesca Uhlmann, Anne van Montfrans, Joris Warnatz, Klaus Williams, Anthony Peter Wood, Phil Kracker, Sven Condliffe, Alison Mary Ehl, Stephan |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Federal Ministry of Education and Research (Germany) Novartis GlaxoSmithKline Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Activated phosphoinositide 3-kinase δ syndrome PIK3CD PIK3R1 Registry Natural history Rapamycin |
| topic |
Activated phosphoinositide 3-kinase δ syndrome PIK3CD PIK3R1 Registry Natural history Rapamycin |
| description |
Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (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. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018 2019 2019 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10261/180501 |
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http://hdl.handle.net/10261/180501 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
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https://doi.org/10.3389/fimmu.2018.00543 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Frontiers Media |
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Frontiers Media |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869408839310245888 |
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15.812455 |