Registry Working Party
The first ESID Registry level 3 project.
The first journal publication resulting from this study has been published in 2018!
Please refer to the ESID Registry Publication list for further details.
Extension of dataset:
We are currently planning on how to amend the database in order to give more space to the assessment of the response to therapy. More information on that will be given here in due time.
Activated PI3-Kinase Delta Syndrome (APDS) is a combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ) – APDS1, or a splice-site mutation in the gene encoding the regulatory subunit p85α – APDS2. Affected patients show a highly variable clinical phenotype in terms of the spectrum of manifestations, the age of onset and the clinical evolution. Recurrent respiratory tract infections and bronchiectasis are the most consistently observed features (>80%), but lymphoproliferation, autoimmunity and increased susceptibility to herpes group virus infections are frequent complications in this disease.
The APDS patient registry has been created to better define the natural history of these rare diseases, to document treatments used in this disorder and to identify predictors for outcome. Moreover, the registry shall be used to offer patients participation in clinical trials based on the use of inhibitors selectively targeting p110δ.
Patients are initially registered with a retrospective case report form and are then documented prospectively every 6 months. The project has been designed for an initial period of 4 years with the goal to recruit 100-200 patients.
The APDS registry project has been initiated by the lead investigators Alison Condliffe (Cambridge, Sheffield), Sven Kracker (Paris) and Stephan Ehl (Freiburg). The project is conducted under the guidance of the ESID registry team and supported by the Clinical Research Unit (“CRU”) of the CCI Freiburg, all of them authorized to act on behalf of ESID.
The project is funded by industry partners. This allows reimbursement of documentation activities for the participating centres (case fees) as well as financing development and maintenance of an ESID registry based online documentation section for APDS patients (level 3) and project management including ethics, data management and quality controls.
Based on informed patient consent, anonymized data from the APDS registry will be made available to industry partners for their purposes (e.g. for designing a drug trial or to include results in regulatory approval). This includes that industry can approach centers contributing to this project to offer their patients participation in a pharmaceutical study.
The ESID Documenting Centers remain in full possession of the registry data and ESID investigators have the right to publish data extracted from the APDS registry at any time – with prior information of the industry partners. Data access and publication rules for this and all other ESID registry projects have been specified and approved by the ESID board.
Participating centers have to be ESID registry documenting centers. If your center is not yet an ESID registry documenting center, please follow the instructions how to join.
To participate in the APDS registry project and receive funding for patient documentation, please contact Annette Uhlmann ( ) to:
- arrange the contract between ESID and the documenting center for this level 3 project
- receive access (password) to the APDS project homepage where you find all documents needed for patient inclusion
- get information on payment conditions for patient registration
- get additional information related to the project
All relevant information and documents for patient inclusion is provided on the APDS project homepage (password protected).
For a quick start all documents relevant for the first steps of patient inclusion can also be found here:
- that the patient has signed the consent for the ESID registry including the consent to forward data to industry partners (ESID consent version 2 or newer, CEREDIH consent version 2010 or newer) – see patient consent section.
- that the patient has been registered in the ESID registry and ESID level 1 dataset has been completed ( new level 1 registration).
ESID project coordination: , Tel. +49 761 270 36961
APDS project coordinator: A. Uhlmann - Tel. +49 761 270 77771
APDS lead investigators:
Alison Condliffe, Sheffield, UK -
Stephan Ehl, Freiburg, Germany –
Sven Kracker, Paris, France -
Angulo, I., O. Vadas, F. Garçon, E. Banham-Hall, V. Plagnol, T.R. Leahy, H. Baxendale, T. Coulter, J. Curtis, C. Wu, K. Blake-Palmer, O. Perisic, D. Smyth, M. Maes, C. Fiddler, J. Juss, D. Cilliers, G. Markelj, A. Chandra, G. Farmer, A. Kielkowska, J. Clark, S. Kracker, M. Debré, C. Picard, I. Pellier, N. Jabado, J.A. Morris, G. Barcenas-Morales, A. Fischer, L. Stephens, P. Hawkins, J.C. Barrett, M. Abinun, M. Clatworthy, A. Durandy, R. Doffinger, E. Chilvers, A.J. Cant, D. Kumararatne, K. Okkenhaug, R.L. Williams, A. Condliffe, and S. Nejentsev. 2013. Phosphoinositide 3-Kinase δ Gene Mutation Predisposes to Respiratory Infection and Airway Damage. Science 34:866-871
Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK, Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA, Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL, Lenardo MJ, Uzel G. 2014. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency. Nat Immunol. 15:88–97.
Kracker, S., J. Curtis, M. A. Ibrahim, A. Sediva, J. Salisbury, V. Campr, M. Debre, J. D. Edgar, K. Imai, C. Picard, J. L. Casanova, A. Fischer, S. Nejentsev, and A. Durandy. 2014. Occurrence of B-cell lymphomas in patients with activated phosphoinositide 3-kinase delta syndrome. The Journal of Allergy and Clinical Immunology 134:233-236.
Deau, M. C., L. Heurtier, P. Frange, F. Suarez, C. Bole-Feysot, P. Nitschke, M. Cavazzana, C. Picard, A. Durandy, A. Fischer, and S. Kracker. 2014. A human immunodeficiency caused by mutations in the PIK3R1 gene. J Clin Invest 124:3923-8.
Lucas, C. L., Y. Zhang, A. Venida, Y. Wang, J. Hughes, J. McElwee, M. Butrick, H. Matthews, S. Price, M. Biancalana, X. Wang, M. Richards, T. Pozos, I. Barlan, A. Ozen, V. K. Rao, H. C. Su, and M. J. Lenardo. 2014. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. J Exp Med 211:2537-47.