Maccari, ME;
Abolhassani, H;
Aghamohammadi, A;
Aiuti, A;
Aleinikova, O;
Bangs, C;
Baris, S;
... Ehl, S; + view all
(2018)
Disease evolution and response to rapamycin in Activated Phosphoinositide 3-Kinase delta syndrome: the european society for immunodeficiencies-Activated Phosphoinositide 3-Kinase d syndrome registry.
Frontiers in Immunology
, 9
, Article 543. 10.3389/fimmu.2018.00543.
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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.pdf - Published Version Download (654kB) | Preview |
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.
| Type: | Article |
|---|---|
| Title: | Disease evolution and response to rapamycin in Activated Phosphoinositide 3-Kinase delta syndrome: the european society for immunodeficiencies-Activated Phosphoinositide 3-Kinase d syndrome registry |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2018.00543 |
| Publisher version: | http://dx.doi.org/10.3389/fimmu.2018.00543 |
| Language: | English |
| Additional information: | © 2018 Maccari, Abolhassani, Aghamohammadi, Aiuti, Aleinikova, Bangs, Baris, Barzaghi, Baxendale, Buckland, Burns, Cancrini, Cant, Cathébras, Cavazzana, Chandra, Conti, Coulter, Devlin, Edgar, Faust, Fischer, Prat, Hammarström, Heeg, Jolles, Karakoc-Aydiner, Kindle, Kiykim, Kumararatne, Grimbacher, Longhurst, Mahlaoui, Milota, Moreira, Moshous, Mukhina, Neth, Neven, Nieters, Olbrich, Ozen, Schmid, Picard, Prader, Rae, Reichenbach, Rusch, Savic, Scarselli, Scheible, Sediva, Sharapova, Shcherbina, Slatter, Soler-Palacin, Stanislas, Suarez, Tucci, Uhlmann, van Montfrans, Warnatz, Williams, Wood, Kracker, Condliffe and Ehl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Immunology, activated phosphoinositide 3-kinase delta syndrome, PIK3CD, PIK3R1, registry, natural history, rapamycin, AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, MUTATION, PI3K, SIROLIMUS, COHORT, GENE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10047305 |
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