Patients with mutations in the XIAP/BIRC4 gene
Organizational Data
- DRKS-ID:
- DRKS00004592
- Recruitment Status:
- Recruiting complete, study complete
- Date of registration in DRKS:
- 2013-01-25
- Last update in DRKS:
- 2020-10-02
- Registration type:
- Retrospective
Acronym/abbreviation of the study
XIAP
URL of the study
http://www.uniklinik-freiburg.de/cci/live/klinische-studien/xiap_en.html
Brief summary in lay language
Scientific study which investigates the functional consequences of mutations in the BIRC4 gene in XIAP deficient patients. The spectrum of clinical features we are interested in includes haemophagocytic lymphohistiocytosis (HLH), inflammatory bowel disease (e.g. Crohn-like disese), unexplained splenomegaly with and without hypogammaglobulinemia, periodic fevers or prolonged mononucleosis.Through functional analysis of the mutated XIAP molecule we aim to understand how the XIAP molecule works in vivo and which XIAP dependent signalling pathways are important in human immune cells. To study the impact of disease associated mutations in BIRC4 on the signals sent when NOD2 and RIG-I are activated, we use cells from affected patients. This enables us to obtain detailed information regarding the molecular consequence of the mutations. By obtaining detailed information about what happens to the XIAP protein when it is mutated and how this affects the processes in which XIAP functions, we hope to obtain understanding of what goes “wrong” in the immune cells of affected patients. On the long run, this can reveal which processes in the cell could be targeted to counterbalance the defects caused by BIRC4 mutations for future treatment. The following centers are involved: CCI Freiburg (cohort coordination and immunological diagnostics), Children's Hospital University Hamburg (genetics), Department for Transfusion Medicine, University Hospital Ulm (genetics) and Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen (functional XIAP analysis)
Brief summary in scientific language
Expression und Funktion des XIAP Moleküls in Patienten mit Mutationen in BIRC4
Health condition or problem studied
- ICD10:
- D82.3 - Immunodeficiency following hereditary defective response to Epstein-Barr virus
- ICD10:
- K50.9 - Crohn disease, unspecified
- ICD10:
- D80.0 - Hereditary hypogammaglobulinaemia
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- Arm 1:
- Patients with XLP, M. Crohn, EBV-infection, splenomegaly, hypogammaglobulinaemia and/or other symptoms for which a mutation in the gene BIRC4/XIAP was diagnosed. Enrolled patients will receive a venipuncture. Isolated patients cells are then flow cytometrically and genetically analyzed. Moreover, we establish cell lines to perform signalling pathway studies.
Endpoints
- Primary outcome:
- Influence of different mutations in XIAP/BIRC4 on intracellular signalling
- Secondary outcome:
- Not applicable
Study Design
- Purpose:
- Diagnostic
- Retrospective/prospective:
- No Entry
- Study type:
- Non-interventional
- Longitudinal/cross-sectional:
- No Entry
- Study type non-interventional:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting complete, study complete
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- University medical center Freiburg im Breisgau
Recruitment period and number of participants
- Planned study start date:
- No Entry
- Actual study start date:
- 2012-05-21
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- 2018-01-15
- Target Sample Size:
- 30
- Final Sample Size:
- 30
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- no minimum age
- Maximum Age:
- no maximum age
- Additional Inclusion Criteria:
- - patients with XLP-2 disease for whom a mutation in gene BIRC4/XIAP was diagnosed - signed consent from the patient/parents for underaged patients
Exclusion Criteria
- lack of signed consent from the patient/parents for underaged patients
Addresses
Primary Sponsor
- Address:
- Universitätsklinikum Freiburg Centrum für Chronische Immundefizienz (CCI)Prof. Dr. med. Stephan EhlBreisacher Str. 117c79106 FreiburgGermany
- Telephone:
- +49 761 270 77300
- Fax:
- +49 761 270 77600
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.uniklinik-freiburg.de/cci/live/index.html
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Universitätsklinikum Freiburg Centrum für Chronische Immundefizienz (CCI)Dr. med. Casten SpeckmannBreisacher Str. 117c79106 FreiburgGermany
- Telephone:
- +49 761 270 43090
- Fax:
- +49 761 270 45990
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.uniklinik-freiburg.de/cci/live/index.html
Contact for Public Queries
- Address:
- Universitätsklinikum Freiburg Centrum für Chronische Immundefizienz (CCI)Dr. med. Casten SpeckmannBreisacher Str. 117c79106 FreiburgGermany
- Telephone:
- +49 761 270 43090
- Fax:
- +49 761 270 45990
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.uniklinik-freiburg.de/cci/live/index.html
Principal Investigator
- Address:
- Universitätsklinikum Freiburg Centrum für Chronische Immundefizienz (CCI)Dr. med. Casten SpeckmannBreisacher Str. 117c79106 FreiburgGermany
- Telephone:
- +49 761 270 43090
- Fax:
- +49 761 270 45990
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.uniklinik-freiburg.de/cci/live/index.html
Sources of Monetary or Material Support
Institutional budget, no external funding (budget of sponsor/PI)
- Address:
- Universitätsklinikum Freiburg Centrum für Chronische Immundefizienz (CCI)Breisacher Str. 117c79106 FreiburgGermany
- Telephone:
- +49 761 270 77300
- Fax:
- +49 761 270 77600
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.uniklinik-freiburg.de/cci/live/index.html
Ethics Committee
Address Ethics Committee
- Address:
- Ethik-Kommission der Albert-Ludwigs-Universität FreiburgEngelberger Str. 2179106 FreiburgGermany
- Telephone:
- +49-761-27072600
- Fax:
- +49-761-27072630
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2012-04-05
- Ethics committee number:
- 143/12
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2012-04-13
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- Steele CL, Doré M, Ammann S, Loughrey M, Montero A, Burns SO, Morris EC, Gaspar B, Gilmour K, Bibi S, Shendi H, Devlin L, Speckmann C, Edgar DM X-linked Inhibitor of Apoptosis Complicated by Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) and Granulomatous Hepatitis. J Clin Immunol. 2016 Oct; 36(7):733-8. doi: 10.1007/s10875-016-0320-3. Epub 2016 Aug 5
- Christiansen M, Ammann S, Speckmann C, Mogensen TH XIAP deficiency and MEFV variants resulting in an autoinflammatory lymphoproliferative syndrome. BMJ Case Rep. 2016 Sep 28; 2016. pii: bcr2016216922. doi: 10.1136/bcr-2016-216922
- Dziadzio M, Ammann S, Canning C, Boyle F, Hassan A, Cale C, Elawad M, Fiil BK, Gyrd-Hansen M, Salzer U, Speckmann C, Grimbacher B Symptomatic males and female carriers in a large Caucasian kindred with XIAP deficiency. J Clin Immunol. 2015 Jul; 35(5):439-44. doi: 10.1007/s10875-015-0166-0. Epub 2015 May 6
- S. Ammann, R. Elling, M. Gyrd-Hansen, G. Dückers, R. Bredius, S.O. Burns, et al., A new functional assay for the diagnosis of X-linked inhibitor of apoptosis (XIAP) deficiency, Clin Exp Immunol. (2014) n/a–n/a. doi:10.1111/cei.12306
- C. Speckmann, S. Ehl, XIAP deficiency is a mendelian cause of late-onset IBD, Gut. (2013) gutjnl–2013–306474. doi:10.1136/gutjnl-2013-306474
- C. Speckmann, K. Lehmberg, M.H. Albert, R.B. Damgaard, M. Fritsch, M. Gyrd-Hansen, et al., X-linked inhibitor of apoptosis (XIAP) deficiency: The spectrum of presenting manifestations beyond hemophagocytic lymphohistiocytosis, Clin Immunol. 149 (2013) 133–141. doi:10.1016/j.clim.2013.07.004
- R.B. Damgaard, B.K. Fiil, C. Speckmann, M. Yabal, U.Z. Stadt, S. Bekker-Jensen, et al., Disease-causing mutations in the XIAP BIR2 domain impair NOD2-dependent immune signalling, EMBO Mol Med. (2013). doi:10.1002/emmm.201303090
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry