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Analysis of RAG-dependent immunodeficiency and autoimmunity

English title Analysis of RAG-dependent immunodeficiency and autoimmunity
Applicant Recher Mike
Number 144863
Funding scheme SNSF Professorships
Research institution Departement Biomedizin Universität Basel
Institution of higher education University of Basel - BS
Main discipline Immunology, Immunopathology
Start/End 01.01.2014 - 31.12.2017
Approved amount 1'606'338.00
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Keywords (6)

Primary Immunodeficiency; Recombination activating gene; VSV; Autoantibodies; Autoimmunity; LCMV

Lay Summary (German)

Lead
Primäre Immundefizienzen sind genetisch determinierte Erkrankungen des Menschen, welche einer Infektneigung zugrundeliegen koennen. Da ein normal arbeitendes Immunsystem auch für eine Toleranz gegen eigenes Körpergewebe notwendig ist, kann sich eine Immundefizienz auch als Autoimmunität (Immunantwort gegen Selbst) äussern.
Lay summary

Ziel dieses Forschungsprojektes ist es, mehr über die Zusammenhänge zwischen primärer Immundefizienz und Autoimmunität heraus zu finden.

 

Ziele des Forschungsprojektes:

Fü diese Fragestellung verwenden wir Mausmodelle, die durch eine mehr oder weniger gravierende (graduelle) genetische Störung im RAG (Recombination Activating Gene) Gen eine mehr oder schwerwiegende Störung der Lymphozytenproduktion  aufweisen.

 

1. Wir beobachten autoimmunologische Reaktionen bei Mäusen mit graduell reduzierter RAG Funktion.

2. Parallel dazu testen wir experimentell die Fähigkeit dieser Mäuse, verschiedene Viruserreger zu eliminieren.

3. Wir beobachten, ob Persistenz eines infektiösen Erregers in Mäusen mit graduell reduzierter RAG Funktion Autoimmunphänomene beeinflusst, oder deren Auftreten gar erst induziert.

 

Wissenschaftlicher Kontext:

Autoimmunerkrankungen beim Menschen sind häufig und deren Ursache(n) im klinischen Alltag bleiben oft ungeklärt. Dieses Forschungsprojekt soll dazu beitragen, eine allfällig zugrunde liegende Immundefizienz bei Patienten mit Autoimmunerkrankungen zu erkennen. Aus dieser Erkenntnis kann eine geeignete immunologische Therapie abgeleitet werden, um den Therapieerfolg zu erhöhen und Therapie-verursachte Komplikationen zu minimieren.


Direct link to Lay Summary Last update: 28.10.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8 + T Cells
Bantug Glenn R., Fischer Marco, Grählert Jasmin, Balmer Maria L., Unterstab Gunhild, Develioglu Leyla, Steiner Rebekah, Zhang Lianjun, Costa Ana S.H., Gubser Patrick M., Burgener Anne-Valérie, Sauder Ursula, Löliger Jordan, Belle Réka, Dimeloe Sarah, Lötscher Jonas, Jauch Annaïse, Recher Mike, Hönger Gideon, Hall Michael N., Romero Pedro, Frezza Christian, Hess Christoph (2018), Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8 + T Cells, in Immunity, 1074.
Varicella Zoster Virus-Specific T Cell Responses in Untreated Giant Cell Arteritis: Comment on the Article by England et al
Bigler Marc B., Hirsiger Julia R., Recher Mike, Mehling Matthias, Daikeler Thomas, Berger Christoph T. (2018), Varicella Zoster Virus-Specific T Cell Responses in Untreated Giant Cell Arteritis: Comment on the Article by England et al, in Arthritis & Rheumatology, 70(2), 318-320.
Interleukin-6 flags infection in tocilizumab-treated giant cell arteritis.
Berger Christoph T, Recher Mike, Daikeler Thomas (2018), Interleukin-6 flags infection in tocilizumab-treated giant cell arteritis., in Rheumatology (Oxford, England), 57(1), 196-197.
[18F]FDG positron emission tomography in patients presenting with suspicion of giant cell arteritis-lessons from a vasculitis clinic.
Imfeld Stephan, Rottenburger Christof, Schegk Elke, Aschwanden Markus, Juengling Freimut, Staub Daniel, Recher Mike, Kyburz Diego, Berger Christoph T, Daikeler Thomas (2017), [18F]FDG positron emission tomography in patients presenting with suspicion of giant cell arteritis-lessons from a vasculitis clinic., in European heart journal cardiovascular Imaging, 0.
Vedolizumab as a successful treatment of CTLA-4-associated autoimmune enterocolitis.
Navarini Alexander A, Hruz Petr, Berger Christoph T, Hou Tie Zheng, Schwab Charlotte, Gabrysch Annemarie, Higgins Rebecca, Frede Natalie, Padberg Sgier Barbara-Christina, Kämpe Olle, Burgener Anne-Valérie, Marquardsen Florian, Baldin Fabian, Bigler Marc, Kistner Anne, Jauch Annaise, Bignucolo Olivier, Meyer Benedikt, Meienberg Fabian, Mehling Matthias, Jeker Lukas T, Heijnen Ingmar, Daikeler Thomas D, Gebbers Jan-Olaf, Grimbacher Bodo (2017), Vedolizumab as a successful treatment of CTLA-4-associated autoimmune enterocolitis., in Journal of Allergy and Clinical Immunology, 1043.
Low immunoglobulin E flags two distinct types of immune dysregulationTwo types of low-IgE immune dysregulation
Elkuch M., Greiff V., Berger C. T., Bouchenaki M., Daikeler T., Bircher A., Navarini A. A., Heijnen I., Recher M. (2017), Low immunoglobulin E flags two distinct types of immune dysregulationTwo types of low-IgE immune dysregulation, in Clinical & Experimental Immunology, 187(3), 345-352.
CD169(+) macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection.
Shabaani Namir, Duhan V, Khairnar V, Gassa A, Ferrer-Tur R, Häussinger D, Recher M, Zelinskyy G, Liu J, Dittmer U, Trilling M, Scheu S, Hardt C, Lang PA, Honke N, Lang KS (2016), CD169(+) macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection., in Cell Death and Disease, e2446.
macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection.
Shaabani Namir, Duhan Vikas, Khairnar Vishal, Gassa Asmae, Ferrer-Tur Rita, Häussinger Dieter, Recher Mike, Zelinskyy Gennadiy, Liu Jia, Dittmer Ulf, Trilling Mirko, Scheu Stefanie, Hardt Cornelia, Lang Philipp A, Honke Nadine, Lang Karl S (2016), macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection., in Cell death & disease, 7(11), 2446-2446.
Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function.
Balmer ML, Ma EH, Bantug GR, Grählert J, Pfister S, Glatter T, Jauch A, Dimeloe S, Slack E, Dehio P, Krzyzaniak MA, King CG, Burgener AV, Fischer M, Develioglu L, Belle R, Recher M, Bonilla WV, Macpherson AJ, Hapfelmeier S, Jones RG, Hess C (2016), Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function., in Immunity, 1312.
A ‘Too Negative’ ANA Test Predicts Antibody Deficiency
Recher Mike, Berger Christoph T., Daikeler Thomas, Hess Christoph, Heijnen Ingmar A. F. M. (2016), A ‘Too Negative’ ANA Test Predicts Antibody Deficiency, in Journal of Clinical Immunology, 36(4), 374-376.
Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8(+) T-cell priming and viral control.
Duhan Vikas, Khairnar Vishal, Friedrich Sarah-Kim, Zhou Fan, Gassa Asmae, Honke Nadine, Shaabani Namir, Gailus Nicole, Botezatu Lacramioara, Khandanpour Cyrus, Dittmer Ulf, Häussinger Dieter, Recher Mike, Hardt Cornelia, Lang Philipp A, Lang Karl S (2016), Virus-specific antibodies allow viral replication in the marginal zone, thereby promoting CD8(+) T-cell priming and viral control., in Scientific reports, 6, 19191-19191.
Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN-I responses.
Honke Nadine, Shaabani Namir, Merches Katja, Gassa Asmae, Kraft Anke, Ehrhardt Katrin, Häussinger Dieter, Löhning Max, Dittmer Ulf, Hengel Hartmut, Recher Mike, Lang Philipp A, Lang Karl S (2016), Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN-I responses., in European journal of immunology, 46(2), 372-80.
N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome.
Volpi Stefano, Santori Elettra, Abernethy Katrina, Mizui Masayuki, Dahlberg Carin I M, Recher Mike, Capuder Kelly, Csizmadia Eva, Ryan Douglas, Mathew Divij, Tsokos George C, Snapper Scott, Westerberg Lisa S, Thrasher Adrian J, Candotti Fabio, Notarangelo Luigi D (2016), N-WASP is required for B-cell-mediated autoimmunity in Wiskott-Aldrich syndrome., in Blood, 127(2), 216-20.
Two separate mechanisms of enforced viral replication balance innate and adaptive immune activation.
Shaabani Namir, Khairnar Vishal, Duhan Vikas, Zhou Fan, Tur Rita Ferrer, Häussinger Dieter, Recher Mike, Tumanov Alexei V, Hardt Cornelia, Pinschewer Daniel, Christen Urs, Lang Philipp A, Honke Nadine, Lang Karl S (2016), Two separate mechanisms of enforced viral replication balance innate and adaptive immune activation., in Journal of autoimmunity, 67, 82-9.
Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency
Walter Jolan E., Rosen Lindsey B., Csomos Krisztian, Rosenberg Jacob M., Mathew Divij, Keszei Marton, Ujhazi Boglarka, Chen Karin, Lee Yu Nee, Tirosh Irit, Dobbs Kerry, Al-Herz Waleed, Cowan Morton J., Puck Jennifer, Bleesing Jack J., Grimley Michael S., Malech Harry, De Ravin Suk See, Gennery Andrew R., Abraham Roshini S., Joshi Avni Y., Boyce Thomas G., Butte Manish J., Nadeau Kari C., Balboni Imelda, Sullivan Kathleen E., Akhter Javeed, Adeli Mehdi, El-Feky Reem A., El-Ghoneimy Dalia H., Dbaibo Ghassan, Wakim Rima, Azzari Chiara, Palma Paolo, Cancrini Caterina, Capuder Kelly, Condino-Neto Antonio, Costa-Carvalho Beatriz T., Oliveira Joao Bosco, Roifman Chaim, Buchbinder David, Kumanovics Attila, Luis Franco Jose, Niehues Tim, Schuetz Catharina, Kuijpers Taco, Yee Christina, Chou Janet, Masaad Michel J., Geha Raif, Uze Gulbu, Gelman Rebecca, Holland Steven M., Recher Mike, Utz Paul J., Browne Sarah K., Notarangelo Luigi D. (2015), Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency, in JOURNAL OF CLINICAL INVESTIGATION, 125(11), 4135-4148.
IFN-gamma licenses CD11b(+) cells to induce progression of systemic lupus erythematosus
Shaabani Namir, Honke Nadine, Dolff Sebastian, Goerg Boris, Khairnar Vishal, Merches Katja, Duhan Vikas, Metzger Sabine, Recher Mike, Barthuber Carmen, Hardt Cornelia, Proksch Peter, Haeussinger Dieter, Witzke Oliver, Lang Philipp A., Lang Karl S. (2015), IFN-gamma licenses CD11b(+) cells to induce progression of systemic lupus erythematosus, in JOURNAL OF AUTOIMMUNITY, 62, 11-21.
Neutralization of colony-stimulating factor 1 receptor prevents sickness behavior syndrome by reprogramming inflammatory monocytes to produce IL-10
Mueller Andreas Felix, Strauss Laura, Greter Melanie, Gast Heidemarie, Recher Mike, Becher Burkhard, Fontana Adriano (2015), Neutralization of colony-stimulating factor 1 receptor prevents sickness behavior syndrome by reprogramming inflammatory monocytes to produce IL-10, in BRAIN BEHAVIOR AND IMMUNITY, 48, 78-85.
Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection
Merches Katja, Khairnar Vishal, Knuschke Torben, Shaabani Namir, Honke Nadine, Duhan Vikas, Recher Mike, Navarini Alexander A., Hardt Cornelia, Haeussinger Dieter, Tuemmler Burkhard, Gulbins Erich, Futerman Anthony H., Hoffmann Daniel, Lang Florian, Lang Philipp A., Westendorf Astrid M., Lang Karl S. (2015), Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection, in CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 36(6), 2379-2392.
Deficiency of the B Cell-Activating Factor Receptor Results in Limited CD169(+) Macrophage Function during Viral Infection
Xu Haifeng C., Huang Jun, Khairnar Vishal, Duhan Vikas, Pandyra Aleksandra A., Grusdat Melanie, Shinde Prashant, McIlwain David R., Maney Sathish Kumar, Gommerman Jennifer, Loehning Max, Ohashi Pamela S., Mak Tak W., Pieper Kathrin, Sic Heiko, Speletas Matthaios, Eibel Hermann, Ware Carl F., Tumanov Alexei V., Kruglov Andrey A., Nedospasov Sergei A., Haeussinger Dieter, Recher Mike, Lang Karl S., Lang Philipp A. (2015), Deficiency of the B Cell-Activating Factor Receptor Results in Limited CD169(+) Macrophage Function during Viral Infection, in JOURNAL OF VIROLOGY, 89(9), 4748-4759.
Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency
Wehr Claudia, Gennery Andrew R., Lindemans Caroline, Schulz Ansgar, Hoenig Manfred, Marks Reinhard, Recher Mike, Gruhn Bernd, Holbro Andreas, Heijnen Ingmar, Meyer Deborah, Grigoleit Goetz, Einsele Hermann, Baumann Ulrich, Witte Thorsten, Sykora Karl-Walter, Goldacker Sigune, Regairaz Lorena, Aksoylar Serap, Ardeniz Omur, Zecca Marco, Zdziarski Przemyslaw, Meyts Isabelle, Matthes-Martin Susanne, Imai Kohsuke, Kamae Chikako, Fielding Adele, Seneviratne Suranjith, Mahlaoui Nizar, Slatter Mary A., Gungor Tayfun, Arkwright Peter D., van Montfrans Joris, Sullivan Kathleen E., Grimbacher Bodo, Cant Andrew, Peter Hans-Hartmut, Finke Juergen, Gaspar H. Bobby, Warnatz Klaus, Rizzi Marta (2015), Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency, in JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 135(4), 988-988.
CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production
Khairnar Vishal, Duhan Vikas, Maney Sathish Kumar, Honke Nadine, Shaabani Namir, Pandyra Aleksandra A., Seifert Marc, Pozdeev Vitaly, Xu Haifeng C., Sharma Piyush, Baldin Fabian, Marquardsen Florian, Merches Katja, Lang Elisabeth, Kirschning Carsten, Westendorf Astrid M., Hauessinger Dieter, Lang Florian, Dittmer Ulf, Kueppers Ralf, Recher Mike, Hardt Cornelia, Scheffrahn Inka, Beauchemin Nicole, Goethert Joachim R., Singer Bernhard B., Lang Philipp A., Lang Karl S. (2015), CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production, in NATURE COMMUNICATIONS, 6, 6217.
Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection
Berger Christoph T., Greiff Victor, Mehling Matthias, Fritz Stefanie, Meier Marc A., Hoenger Gideon, Conen Anna, Recher Mike, Battegay Manuel, Reddy Sai T., Hess Christoph (2015), Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection, in HUMAN VACCINES & IMMUNOTHERAPEUTICS, 11(2), 391-396.
Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency.
Walter Jolan E, Rosen Lindsey B, Csomos Krisztian, Rosenberg Jacob M, Mathew Divij, Keszei Marton, Ujhazi Boglarka, Chen Karin, Lee Yu Nee, Tirosh Irit, Dobbs Kerry, Al-Herz Waleed, Cowan Morton J, Puck Jennifer, Bleesing Jack J, Grimley Michael S, Malech Harry, De Ravin Suk See, Gennery Andrew R, Abraham Roshini S, Joshi Avni Y, Boyce Thomas G, Butte Manish J, Nadeau Kari C, Balboni Imelda (2015), Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency., in The Journal of clinical investigation, 125(11), 4135-48.
CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production.
Khairnar Vishal, Duhan Vikas, Maney Sathish Kumar, Honke Nadine, Shaabani Namir, Pandyra Aleksandra A, Seifert Marc, Pozdeev Vitaly, Xu Haifeng C, Sharma Piyush, Baldin Fabian, Marquardsen Florian, Merches Katja, Lang Elisabeth, Kirschning Carsten, Westendorf Astrid M, Häussinger Dieter, Lang Florian, Dittmer Ulf, Küppers Ralf, Recher Mike, Hardt Cornelia, Scheffrahn Inka, Beauchemin Nicole, Göthert Joachim R (2015), CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production., in Nature communications, 6, 6217-6217.
Deficiency of the B cell-activating factor receptor results in limited CD169+ macrophage function during viral infection.
Xu Haifeng C, Huang Jun, Khairnar Vishal, Duhan Vikas, Pandyra Aleksandra A, Grusdat Melanie, Shinde Prashant, McIlwain David R, Maney Sathish Kumar, Gommerman Jennifer, Löhning Max, Ohashi Pamela S, Mak Tak W, Pieper Kathrin, Sic Heiko, Speletas Matthaios, Eibel Hermann, Ware Carl F, Tumanov Alexei V, Kruglov Andrey A, Nedospasov Sergei A, Häussinger Dieter, Recher Mike, Lang Karl S, Lang Philipp A (2015), Deficiency of the B cell-activating factor receptor results in limited CD169+ macrophage function during viral infection., in Journal of virology, 89(9), 4748-59.
Diagnosis at your fingertips: splinters and microemboli - is it SLE?
Berger CT, Baldi T, Aschwanden M, Scherer K, Recher M, Hess C, Daikeler T (2015), Diagnosis at your fingertips: splinters and microemboli - is it SLE?, in Lupus, 341.
Diagnosis at your fingertips: splinters and microemboli--is it SLE?
Berger C T, Baldi T, Aschwanden M, Scherer K, Recher M, Hess C, Daikeler T (2015), Diagnosis at your fingertips: splinters and microemboli--is it SLE?, in Lupus, 24(3), 341-2.
IFN-γ licenses CD11b(+) cells to induce progression of systemic lupus erythematosus.
Shaabani Namir, Honke Nadine, Dolff Sebastian, Görg Boris, Khairnar Vishal, Merches Katja, Duhan Vikas, Metzger Sabine, Recher Mike, Barthuber Carmen, Hardt Cornelia, Proksch Peter, Häussinger Dieter, Witzke Oliver, Lang Philipp A, Lang Karl S (2015), IFN-γ licenses CD11b(+) cells to induce progression of systemic lupus erythematosus., in Journal of autoimmunity, 62, 11-21.
Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection.
Berger Christoph T, Greiff Victor, Mehling Matthias, Fritz Stefanie, Meier Marc A, Hoenger Gideon, Conen Anna, Recher Mike, Battegay Manuel, Reddy Sai T, Hess Christoph (2015), Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection., in Human vaccines & immunotherapeutics, 11(2), 391-6.
Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency.
Wehr Claudia, Gennery Andrew R, Lindemans Caroline, Schulz Ansgar, Hoenig Manfred, Marks Reinhard, Recher Mike, Gruhn Bernd, Holbro Andreas, Heijnen Ingmar, Meyer Deborah, Grigoleit Goetz, Einsele Hermann, Baumann Ulrich, Witte Thorsten, Sykora Karl-Walter, Goldacker Sigune, Regairaz Lorena, Aksoylar Serap, Ardeniz Ömur, Zecca Marco, Zdziarski Przemyslaw, Meyts Isabelle, Matthes-Martin Susanne, Imai Kohsuke (2015), Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency., in The Journal of allergy and clinical immunology, 135(4), 988-997.
Neutralization of colony-stimulating factor 1 receptor prevents sickness behavior syndrome by reprogramming inflammatory monocytes to produce IL-10.
Müller Andreas Felix, Strauss Laura, Greter Melanie, Gast Heidemarie, Recher Mike, Becher Burkhard, Fontana Adriano (2015), Neutralization of colony-stimulating factor 1 receptor prevents sickness behavior syndrome by reprogramming inflammatory monocytes to produce IL-10., in Brain, behavior, and immunity, 48, 78-85.
Risk factors for pneumocystis pneumonia in giant cell arteritis: a single-centre cohort study.
Berger C T, Greiff V, John S, Koenig K F, Bigler M B, Recher M, Hess C, Daikeler T (2015), Risk factors for pneumocystis pneumonia in giant cell arteritis: a single-centre cohort study., in Clinical and experimental rheumatology, 33(2 Suppl 89), 122-5.
Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels.
Bigler Marc B, Egli Simon B, Hysek Cédric M, Hoenger Gideon, Schmied Laurent, Baldin Fabian S, Marquardsen Florian A, Recher Mike, Liechti Matthias E, Hess Christoph, Berger Christoph T (2015), Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels., in PloS one, 10(12), 0145635-0145635.
The Swiss National Registry for Primary Immunodeficiencies: report on the first 6 years' activity from 2008 to 2014.
Marschall K, Hoernes M, Bitzenhofer-Grüber M, Jandus P, Duppenthaler A, Wuillemin W A, Rischewski J, Boyman O, Heininger U, Hauser T, Steiner U, Posfay-Barbe K, Seebach J, Recher M, Hess C, Helbling A, Reichenbach J, Reichenbach J (2015), The Swiss National Registry for Primary Immunodeficiencies: report on the first 6 years' activity from 2008 to 2014., in Clinical and experimental immunology, 182(1), 45-50.
Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection.
Lang P A, Meryk A, Pandyra A A, Brenner D, Brüstle A, Xu H C, Merches K, Lang F, Khairnar V, Sharma P, Funkner P, Recher M, Shaabani N, Duncan G S, Duhan V, Homey B, Ohashi P S, Häussinger D, Knolle P A, Honke N, Mak T W, Lang K S (2015), Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection., in Cell death and differentiation, 22(1), 164-73.
Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection.
Merches Katja, Khairnar Vishal, Knuschke Torben, Shaabani Namir, Honke Nadine, Duhan Vikas, Recher Mike, Navarini Alexander A, Hardt Cornelia, Häussinger Dieter, Tümmler Burkhard, Gulbins Erich, Futerman Anthony H, Hoffmann Daniel, Lang Florian, Lang Philipp A, Westendorf Astrid M, Lang Karl S (2015), Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection., in Cellular physiology and biochemistry : international journal of experimental cellular physiology, bi, 36(6), 2379-92.
Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells
Bouma Gerben, Carter Natalie A., Recher Mike, Malinova Dessislava, Adriani Marsilio, Notarangelo Luigi D., Burns Siobhan O., Mauri Claudia, Thrasher Adrian J. (2014), Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells, in EUROPEAN JOURNAL OF IMMUNOLOGY, 44(9), 2692-2702.
Genetic variation in schlafen genes in a patient with a recapitulation of the murine Elektra phenotype
Recher Mike, Karjalainen-Lindsberg Marja-Liisa, Lindlof Mikael, Soderlund-Venermo Maria, Lanzi Gaetana, Vaisanen Elina, Kumar Arun, Sadeghi Mohammadreza, Berger Christoph T., Alitalo Tiina, Anttila Pekka, Kolehmainen Maija, Franssila Rauli, Chen Tingting, Siitonen Sanna, Delmonte Ottavia M., Walter Jolan E., Pessach Itai, Hess Christoph, Simpson Michael A., Navarini Alexander A., Giliani Silvia, Hedman Klaus, Seppanen Mikko, Notarangelo Luigi D. (2014), Genetic variation in schlafen genes in a patient with a recapitulation of the murine Elektra phenotype, in JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 133(5), 1462-1462.
A common single nucleotide polymorphism impairs B-cell activating factor receptor's multimerization, contributing to common variable immunodeficiency
Pieper Kathrin, Rizzi Marta, Speletas Matthaios, Smulski Cristian R., Sic Heiko, Kraus Helene, Salzer Ulrich, Fiala Gina J., Schamel Wolfgang W., Lougaris Vassilios, Plebani Alessandro, Hammarstrom Lennart, Recher Mike, Germenis Anastasios E., Grimbacher Bodo, Warnatz Klaus, Rolink Antonius G., Schneider Pascal, Notarangelo Luigi D., Eibel Hermann (2014), A common single nucleotide polymorphism impairs B-cell activating factor receptor's multimerization, contributing to common variable immunodeficiency, in JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 133(4), 1222-1225.
A common single nucleotide polymorphism impairs B-cell activating factor receptor's multimerization, contributing to common variable immunodeficiency
Pieper Kathrin, Rizzi Marta, Speletas Matthaios, Smulski Cristian R., Sic Heiko, Kraus Helene, Salzer Ulrich, Fiala Gina J., Schamel Wolfgang W., Lougaris Vassilios, Plebani Alessandro, Hammarstrom Lennart, Recher Mike, Germenis Anastasios E., Grimbacher Bodo, Warnatz Klaus, Rolink Antonius G., Schneider Pascal, Notarangelo Luigi D., Eibel Hermann (2014), A common single nucleotide polymorphism impairs B-cell activating factor receptor's multimerization, contributing to common variable immunodeficiency, in JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 133(4), 1222-1225.
Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells
Bouma Gerben, Carter Natalie A., Recher Mike, Malinova Dessislava, Adriani Marsilio, Notarangelo Luigi D., Burns Siobhan O., Mauri Claudia, Thrasher Adrian J. (2014), Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells, in EUROPEAN JOURNAL OF IMMUNOLOGY, 44(9), 2692-2702.
Genetic variation in schlafen genes in a patient with a recapitulation of the murine Elektra phenotype
Recher Mike, Karjalainen-Lindsberg Marja-Liisa, Lindlof Mikael, Soderlund-Venermo Maria, Lanzi Gaetana, Vaisanen Elina, Kumar Arun, Sadeghi Mohammadreza, Berger Christoph T., Alitalo Tiina, Anttila Pekka, Kolehmainen Maija, Franssila Rauli, Chen Tingting, Siitonen Sanna, Delmonte Ottavia M., Walter Jolan E., Pessach Itai, Hess Christoph, Simpson Michael A., Navarini Alexander A., Giliani Silvia, Hedman Klaus, Seppanen Mikko, Notarangelo Luigi D. (2014), Genetic variation in schlafen genes in a patient with a recapitulation of the murine Elektra phenotype, in JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 133(5), 1462-1462.
Primary and secondary immunodeficiencies
Cantoni N, Recher M (2014), Primary and secondary immunodeficiencies, in Therapeutische Umschau, 31.

Collaboration

Group / person Country
Types of collaboration
Prof. Donald Bloch, Rheumatology, MGH, Boston, USA United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Luigi D. Notarangelo, Division of Immunology, Childrens Hospital Boston, USA United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Karl S Lang, Institute of Immunology, University of Essen, Germany Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof. Christoph Hess, Departement Biomedizin, Universitaetsspital Basel, Schweiz Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Allergy Immunology Update Talk given at a conference Nebenwirkungen der Immunglobulintherapie 02.02.2018 Grindelwald, Switzerland Recher Mike;
QUALITÄTSZIRKEL FÜR HAUSÄRZTE UND ANDERE FACHÄRZTE Frauenfeld Individual talk Immundefizienz 05.09.2017 Frauenfeld, Switzerland Recher Mike;
QUALITÄTSZIRKEL FÜR HAUSÄRZTE UND ANDERE FACHÄRZTE Solothurnisches Niederamt Individual talk Aktuelle Immunologie 29.08.2017 Lostorf, Switzerland Recher Mike;
Medart Basel 2017 Talk given at a conference Immundefizienz diskutiert anhand mehrerer klinischer Fälle 22.06.2017 Basel, Switzerland Recher Mike;
Allergy Immunology Update Talk given at a conference Immune Dysregulation: Clinical cases and laboratory hints 19.01.2017 Grindelwald, Switzerland Recher Mike;
Differentialdiagnose der Hypogammaglobulinaemie Individual talk Differentialdiagnose der Hypogammaglobulinaemie 19.11.2014 Aarau, Kantonsspital, Switzerland Recher Mike;
Immundefizienz im Erwachsenenalter Individual talk Immundefizienz im Erwachsenenalter 23.10.2014 Bern, Inselspital, Switzerland Recher Mike;
Differentialdiagnose Hypogammaglobulinaemie Individual talk Differentialdiagnose Hypogammaglobulinaemie 28.08.2014 Liestal, Kantonsspital, Switzerland Recher Mike;


Self-organised

Title Date Place
Allergy and Immunology Update, Grindelwald 02.02.2018 Grindelwald, Switzerland
«Gemeinsam vorwärts» – Die Fortbildung für und mit Hausärztinnen und Hausärzten - klinische Immunologie 07.09.2017 Basel, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media New Test for Rare Immunodeficiency UniNews International 2017
Talks/events/exhibitions DBM Open House / Tag der Biomedizin German-speaking Switzerland 2016
Media relations: print media, online media Genetisch bedingte Darmentzündung erfolgreich behandelt UniBasel News International 2016
Media relations: print media, online media Wie man den Winter überlisten kann Zeitschrift Zeitlupe German-speaking Switzerland 2016
Talks/events/exhibitions Immundefizienz und Immunmetabolismus UniNacht 2015 German-speaking Switzerland 2015
Media relations: print media, online media Immundefektplattform Wissenschaftlicher Rat AHA Homepage (Allergiezentrum Schweiz) Italian-speaking Switzerland German-speaking Switzerland Western Switzerland 2014

Awards

Title Year
Müller Gierok Preis für die beste wissneschaftliche Arbeit in Allergologie/klinische Immunologie 2016 2016

Associated projects

Number Title Start Funding scheme
173186 Immune-dysregulation and autoimmunity in primary immunodeficiency 01.01.2018 SNSF Professorships
173186 Immune-dysregulation and autoimmunity in primary immunodeficiency 01.01.2018 SNSF Professorships

Abstract

Primary immunodeficiencies (PID) comprise more than 150 different disorders that affect the development, function -or both- of the immune system due to mutations in immune-related genes. Besides their association with infection, PID are associated with autoimmunity and immune-dysregulation. Autoimmunity is an independent risk factor of mortality in PID patients regardless of immunoglobulin replacement therapy. Since PID are monogenic diseases, the study of autoimmunity in patients or relevant mouse models represents a valuable tool to understand basic mechanisms involved in the induction of autoimmunity. Our preliminary data show that, in humans and murine models, mutations in the recombination activating genes (RAG) as a model PID may lead to different clinical entities ranging from severe combined immunodeficiency to Omenn syndrome or RAG-dependent granuloma that are defined by autoinflammation and autoimmunity, based on the functional severity of the RAG mutation. Using gradual impairment of RAG function in murine models, the here proposed work will address whether and how immunodeficiency and autoimmunity are interlinked. The results of our studies will help to understand which aspects of PID-related autoimmunity are mediated by B vs. T lymphocytes, and what mediators are involved. This may eventually impact the clinical treatment of autoimmunity. The work proposed will also show how infection influences autoimmunity in the setting of PID.
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