Centrum für Chronische Immundefizienz - CCI

The research group „Human T-cell immunodeficiency“ works at the interface of clinical and basic research with a focus on human T cell immunity. The research projects encompass the whole spectrum of translational research from the identification and characterization of novel gene defects followed by pathophysiological studies in mouse models and human patients to the development of novel diagnostic tools and using this basic knowledge in the design of international treatment trials.

CV

Research Areas

T cell immunity is important for the control of most infections. A successful T cell response involves antigen recognition, cellular activation and differentiation, rapid expansion and exertion of eff ector functions. These potent and highly dynamic processes must be tightly regulated in order to avoid inappropriate or uncontrolled infl ammatory responses. Human genetic diseases provide a fascinating window to understand T cell immunity and its relevance for the control of infectious diseases as well as for diseases of immune dysregulation.  

The research group „Genetic deficiencies of human T cell immunity“ works at the interface between clinical and basic immunology with a particular focus on T cell immunity. The research activities cover a large spectrum from basic research in animal models or the identifi cation of new genetic defects to international diagnostic and clinical studies. The group integrates both physicians and basic scientists.  

We study three immunodeficiency states representing models for different aspects of T cell immunity:

Publications

HLH

• Neuroinflammatory Disease as an Isolated Manifestation of Hemophagocytic Lymphohistiocytosis. Blincoe A, Heeg M, Campbell PK, Hines M, Khojah A, Klein-Gitelman M, Talano JA, Speckmann C, Touzot F, Lankester A, Legger GE, Rivière JG, Garcia-Prat M, Alonso L, Putti MC, Lehmberg K, Maier S, El Chazli Y, Elmaksoud MA, Astigarraga I, Kurjane N, Bulina I, Kenina V, Bryceson Y, Rascon J, Lortie A, Goldstein G, Booth C, Worth A, Wassmer E, Schmitt EG, Warren JT, Bednarski JJ, Ali S, Chiang KY, Krueger J, Henry MM, Holland SM, Marsh RA, Ehl S*, Haddad E*. J Clin Immunol. 2020 Aug;40(6):901-916. doi: 10.1007/s10875-020-00814-6. Epub 2020 Jul 7.
   
• Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity. Groß M, Speckmann C, May A, Gajardo-Carrasco T, Wustrau K, Maier SL, Panning M, Huzly D, Agaimy A, Bryceson YT, Choo S, Chow CW, Dückers G, Fasth A, Fraitag S, Gräwe K, Haxelmans S, Holzinger D, Hudowenz O, Hübschen JM, Khurana C, Kienle K, Klifa R, Korn K, Kutzner H, Lämmermann T, Ledig S, Lipsker D, Meeths M, Naumann-Bartsch N, Rascon J, Schänzer A, Seidl M, Tesi B, Vauloup-Fellous C, Vollmer-Kary B, Warnatz K, Wehr C, Neven B, Vargas P, Sepulveda FE, Lehmberg K, Schmitt-Graeff A, Ehl S. J Allergy Clin Immunol. 2022 Jan;149(1):388-399.e4. doi: 10.1016/j.jaci.2021.05.007. Epub 2021 May 24.
   
• NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation. Castro CN, Rosenzwajg M, Carapito R, Shahrooei M, Konantz M, Khan A, Miao Z, Groß M, Tranchant T, Radosavljevic M, Paul N, Stemmelen T, Pitoiset F, Hirschler A, Nespola B, Molitor A, Rolli V, Pichot A, Faletti LE, Rinaldi B, Friant S, Mednikov M, Karauzum H, Aman MJ, Carapito C, Lengerke C, Ziaee V, Eyaid W, Ehl S*, Alroqi F*, Parvaneh N*, Bahram S*. J Exp Med. 2020 Dec 7;217(12):e20192275. doi: 10.1084/jem.20192275.

*equal contribution

P-CID

• Long-term robustness of a T-cell system emerging from somatic rescue of a genetic block in T-cell development. Kury P, Führer M, Fuchs S, Lorenz MR, Giorgetti OB, Bakhtiar S, Frei AP, Fisch P, Boehm T, Schwarz K, Speckmann C, Ehl S. EBioMedicine. 2020 Sep;59:102961. doi: 10.1016/j.ebiom.2020.102961. Epub 2020 Aug 22.
   
• A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis. Speckmann C, Doerken S, Aiuti A, Albert MH, Al-Herz W, Allende LM, Scarselli A, Avcin T, Perez-Becker R, Cancrini C, Cant A, Di Cesare S, Finocchi A, Fischer A, Gaspar HB, Ghosh S, Gennery A, Gilmour K, González-Granado LI, Martinez-Gallo M, Hambleton S, Hauck F, Hoenig M, Moshous D, Neven B, Niehues T, Notarangelo L, Picard C, Rieber N, Schulz A, Schwarz K, Seidel MG, Soler-Palacin P, Stepensky P, Strahm B, Vraetz T, Warnatz K, Winterhalter C, Worth A, Fuchs S, Uhlmann A, Ehl S; P-CID study of the Inborn Errors Working Party of the EBMT. J Allergy Clin Immunol. 2017 Apr;139(4):1302-1310

AL-PID

• Diagnostic evaluation of paediatric autoimmune lymphoproliferative immunodeficiencies (ALPID): a prospective cohort study. Hägele P, Staus P, Scheible R, Uhlmann A, Heeg M, Klemann C, Maccari ME, Ritterbusch H, Armstrong M, Cutcutache I, Elliott KS, von Bernuth H, Leahy TR, Leyh J, Holzinger D, Lehmberg K, Svec P, Masjosthusmann K, Hambleton S, Jakob M, Sparber-Sauer M, Kager L, Puzik A, Wolkewitz M, Lorenz MR, Schwarz K, Speckmann C, Rensing-Ehl A, Ehl S; ALPID study group. Lancet Haematol. 2024 Feb;11(2):e114-e126
   
• Abnormal biomarkers predict complex FAS or FADD defects missed by exome sequencing. Rensing-Ehl A, Lorenz MR, Führer M, Willenbacher W, Willenbacher E, Sopper S, Abinun M, Maccari ME, König C, Haegele P, Fuchs S, Castro C, Kury P, Pelle O, Klemann C, Heeg M, Thalhammer J, Wegehaupt O, Fischer M, Goldacker S, Schulte B, Biskup S, Chatelain P, Schuster V, Warnatz K, Grimbacher B, Meinhardt A, Holzinger D, Oommen PT, Hinze T, Hebart H, Seeger K, Lehmberg K, Leahy TR, Claviez A, Vieth S, Schilling FH, Fuchs I, Groß M, Rieux-Laucat F, Magerus A, Speckmann C, Schwarz K, Ehl S; ALPS Study Group. J Allergy Clin Immunol. 2024 Jan;153(1):297-308
   
• Autoimmune lymphoproliferative immunodeficiencies (ALPIDs): A proposed approach to redefining ALPS and other lymphoproliferative immune disorders. Magerus A, Rensing-Ehl A, Rao VK, Teachey DT, Rieux-Laucat F, Ehl S. J Allergy Clin Immunol. 2024 Jan;153(1):67-76
   
• Combined germline and somatic human FADD mutations cause autoimmune lymphoproliferative syndrome. Pellé O, Moreno S, Lorenz MR, Riller Q, Fuehrer M, Stolzenberg MC, Maccari ME, Lenoir C, Cheminant M, Hinze T, Hebart HF, König C, Schvartz A, Schmitt Y, Vinit A, Henry E, Touzart A, Villarese P, Isnard P, Neveux N, Landman-Parker J, Picard C, Fouyssac F, Neven B, Grimbacher B, Speckmann C, Fischer A, Latour S, Schwarz K, Ehl S, Rieux-Laucat F, Rensing-Ehl A, Magérus A. J Allergy Clin Immunol. 2024 Jan;153(1):203-215
   
• Revisiting autoimmune lymphoproliferative syndrome caused by Fas ligand mutations. Maccari ME, Schneider P, Smulski CR, Meinhardt A, Pinto F, Gonzalez-Granado LI, Schuetz C, Sica MP, Gross M, Fuchs I, Kury P, Heeg M, Vocat T, Willen L, Thomas C, Hühn R, Magerus A, Lorenz M, Schwarz K, Rieux-Laucat F, Ehl S*, Rensing-Ehl A*. J Allergy Clin Immunol. 2023 May;151(5):1391-1401
   
• A distinct CD38+CD45RA+ population of CD4+, CD8+, and double-negative T cells is controlled by FAS. Maccari ME, Fuchs S, Kury P, Andrieux G, Völkl S, Bengsch B, Lorenz MR, Heeg M, Rohr J, Jägle S, Castro CN, Groß M, Warthorst U, König C, Fuchs I, Speckmann C, Thalhammer J, Kapp FG, Seidel MG, Dückers G, Schönberger S, Schütz C, Führer M, Kobbe R, Holzinger D, Klemann C, Smisek P, Owens S, Horneff G, Kolb R, Naumann-Bartsch N, Miano M, Staniek J, Rizzi M, Kalina T, Schneider P, Erxleben A, Backofen R, Ekici A, Niemeyer CM, Warnatz K, Grimbacher B, Eibel H, Mackensen A, Frei AP, Schwarz K, Boerries M, Ehl S*, Rensing-Ehl A*. J Exp Med. 2021 Feb 1;218(2):e20192191. doi: 10.1084/jem.20192191.
   
• Distinct molecular response patterns of activating STAT3 mutations associate with penetrance of lymphoproliferation and autoimmunity. Jägle S, Heeg M, Grün S, Rensing-Ehl A, Maccari ME, Klemann C, Jones N, Lehmberg K, Bettoni C, Warnatz K, Grimbacher B, Biebl A, Schauer U, Hague R, Neth O, Mauracher A, Pachlopnik Schmid J, Fabre A, Kostyuchenko L, Führer M, Lorenz MR, Schwarz K, Rohr J, Ehl S. Clin Immunol. 2020 Jan;210:108316. doi: 10.1016/j.clim.2019.108316. Epub 2019 Nov 23.
   
• Early-onset autoimmunity associated with SOCS1 haploinsufficiency. Hadjadj J, Castro CN, Tusseau M, Stolzenberg MC, Mazerolles F, Aladjidi N, Armstrong M, Ashrafian H, Cutcutache I, Ebetsberger-Dachs G, Elliott KS, Durieu I, Fabien N, Fusaro M, Heeg M, Schmitt Y, Bras M, Knight JC, Lega JC, Lesca G, Mathieu AL, Moreews M, Moreira B, Nosbaum A, Page M, Picard C, Ronan Leahy T, Rouvet I, Ryan E, Sanlaville D, Schwarz K, Skelton A, Viallard JF, Viel S, Villard M, Callebaut I, Picard C, Walzer T, Ehl S, Fischer A, Neven B, Belot A, Rieux-Laucat F. Nat Commun. 2020 Oct 21;11(1):5341. doi: 10.1038/s41467-020-18925-4.

*equal contribution