Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 543 |
| Number of pages | 8 |
| Journal | Frontiers in Immunology |
| Volume | 9 |
| DOIs | |
| Publication status | Published - Mar 16 2018 |
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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 Registry. / The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry.
In: Frontiers in Immunology, Vol. 9, 16.03.2018, p. 543.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome
T2 - The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry
AU - The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry
AU - Maccari, Maria Elena
AU - Abolhassani, Hassan
AU - Aghamohammadi, Asghar
AU - Aiuti, Alessandro
AU - Aleinikova, Olga
AU - Bangs, Catherine
AU - Baris, Safa
AU - Barzaghi, Federica
AU - Baxendale, Helen
AU - Buckland, Matthew
AU - Burns, Siobhan O
AU - Cancrini, Caterina
AU - Cant, Andrew
AU - Cathébras, Pascal
AU - Cavazzana, Marina
AU - Chandra, Anita
AU - Conti, Francesca
AU - Coulter, Tanya
AU - Devlin, Lisa A
AU - Edgar, J David M
AU - Faust, Saul
AU - Fischer, Alain
AU - Garcia-Prat, Marina
AU - Hammarström, Lennart
AU - Heeg, Maximilian
AU - Jolles, Stephen
AU - Karakoc-Aydiner, Elif
AU - Kindle, Gerhard
AU - Kiykim, Ayca
AU - Kumararatne, Dinakantha
AU - Grimbacher, Bodo
AU - Longhurst, Hilary
AU - Mahlaoui, Nizar
AU - Milota, Tomas
AU - Moreira, Fernando
AU - Moshous, Despina
AU - Mukhina, Anna
AU - Neth, Olaf
AU - Neven, Benedicte
AU - Nieters, Alexandra
AU - Olbrich, Peter
AU - Ozen, Ahmet
AU - Pachlopnik Schmid, Jana
AU - Picard, Capucine
AU - Prader, Seraina
AU - Rae, William
AU - Reichenbach, Janine
AU - Rusch, Stephan
AU - Savic, Sinisa
AU - Scarselli, Alessia
PY - 2018/3/16
Y1 - 2018/3/16
N2 - 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.
AB - 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.
U2 - 10.3389/fimmu.2018.00543
DO - 10.3389/fimmu.2018.00543
M3 - Article
C2 - 29599784
VL - 9
SP - 543
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
ER -