Centrum für Chronische Immundefizienz - CCI

Diagnostic evaluation of patients with lymphoproliferation and autoimmunity (autoimmune lymphoproliferative primary immunodefeciency AL-PID) can be challenging. The most common underlying genetic diagnosis is autoimmune lymphoproliferative syndrome (ALPS). Biomarker determination is a useful screening method; the combination of vitamin B12 and sFasL provides the best sensitivity and specificity. Genetic confirmation can be quite challenging because of somatic or intronic mutations. In our diagnostic algorithm we proceed as follows:

• determination of the biomarkers vitamin B12, sFasL
• determination of CD3+TCRab+CD4-CD8- DNT cells and their Fas expression
• if normal results – no further ALPS directed analysis
• if abnormal results – genetic analysis of FAS in granulocyte DNA , if no mutation is found – sort of DNT cells to look for somatic FAS mutations
• if ambiguous results – further tests (including apoptosis testing)

For diagnostic requests, please proceed as follows:

• Contact our Advanced Diagnostics Unit prior to shipment
  Phone: +49 (0)761-270 71010
  Mail: cci.diagnostik@uniklinik-freiburg.de
• Send signed consent form (incl. 'Information Datenschutz'), clinical data sheet and patient blood samples (4 ml serum plus 10 (-15) ml EDTA blood) at room temperature and via overnight express to:
            MEDICAL CENTER - UNIVERSITY OF FREIBURG
            CCI - Advanced Diagnostics Unit
            Breisacher Str. 115 (EG)
            D - 79106 Freiburg, Germany
• For patients with German health insurance: please include „Überweisungsschein“ for laboratory analysis
• For international patients: Please contact us for details

For patients with clinical clues suggesting a diagnosis different from ALPS or patients in whom ALPS has been excluded, we offer additional diagnostic testing on a research basis upon request. Criteria to include a patient into this program are: positive family history, early-onset autoimmunity, immune dysregulation in addition to autoimmune cytopenia, distinct additional immunological abnormalities.

Note: The charged costs (also for German patients with „Überweisungsschein“) do not cover our true expenses for the performed analyses. We can only offer the evaluation, because the analyses are linked to a clinical study, which provides limited funding. Therefore, we request that samples are accompanied by a clinical data sheet and an informed consent sheet of the patient.

Study Documents

Study Inclusion
Patient Information/Consent
AND Initial Data Sheet

Deutsch:

• für Eltern
• für erwachsene Patienten
• für gesunde Probanden

English:

• for parents
• for adult patients
• for healthy subjects

Yearly Follow-up - Data Sheet

• for parents/for adult patients

References

• Klemann C, Esquivel M, Magerus-Chatinet A, Lorenz MR, ..., Ehl S, Rensing-Ehl A, et al., Evolution of disease activity and biomarkers on and off rapamycin in 28 patients with autoimmune lymphoproliferative syndrome, Haematologica. 2017 Feb;102(2):e52-e56. doi: 10.3324/haematol.2016.153411.  
• Völkl S, Rensing-Ehl A, Allgäuer A, Schreiner E, Lorenz MR, Rohr J, et al., Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome, Blood. (2016). pii: blood-2015-11-685024.  
• Janda A, Schwarz K, van der Burg M, Vach W, Ijspeert H, Lorenz MR et al., Disturbed B-lymphocyte selection in autoimmune lymphoproliferative syndrome, Blood. (2016). doi: 10.1182/blood-2015-04-642488.  
• Rensing-Ehl A, Pannicke U, Zimmermann SY, Lorenz MR, Neven B et al., Gray platelet syndrome can mimic autoimmune lymphoproliferative syndrome., Blood. (2015). doi: 10.1182/blood-2015-06-654145.
• A. Rensing-Ehl, S. Völkl, Speckmann, M.R. Lorenz, J. Ritter, A. Janda, et al., Abnormally differentiated CD4+ or CD8+ T-cells with phenotypic and genetic features of double negative T-cells in human Fas deficiency, Blood. (2014). doi:10.1182/blood-2014-03-564286.
• A. Rensing-Ehl, A. Janda, M.R. Lorenz, B.P. Gladstone, I. Fuchs, M. Abinun, et al., Sequential decisions on FAS sequencing guided by biomarkersin patients with lymphoproliferation and autoimmune cytopenia, Haematologica. (2013). doi:10.3324/haematol.2012.081901.
• Janda, A. Rensing-Ehl, H. Eibel, S. Ehl, C. Speckmann, Elevated serum BAFF levels in patients with autoimmunity and lymphoproliferation, Scand J Immunol. (2011). doi:10.1111/j.1365-3083.2011.02597.x.
• A. Rensing-Ehl, K. Warnatz, S. Fuchs, M. Schlesier, U. Salzer, R. Draeger, et al., Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency, Clin Immunol. 137 (2010) 357–365. doi:10.1016/j.clim.2010.08.008.

Contact

Study Coordination
Dr. med. Anne Rensing-Ehl
Tel. +49 (0) 761 270-71080
Fax +49 (0) 761 270-77744
anne.rensing-ehl@uniklinik-freiburg.de  &

PD Dr. med. Carsten Speckmann
Tel. +49 (0) 761 270-43010
Fax +49 (0) 761 270-77744
carsten.speckmann@uniklinik-freiburg.de

Advanced Diagnostics Unit
Miriam Groß
Tel. +49 (0) 761 270-71010
Fax +49 (0) 761 270-96 71 070
miriam.gross@uniklinik-freiburg.de

CCI
MEDICAL CENTER - UNIVERSITY OF FREIBURG
Center for Chronic Immunodeficiency
at Center for Translational Cell Research
Breisacher Str. 115
D-79106 Freiburg