immune-dysregulation; RAG; antibody deficiency; immunodeficiency; autoimmunity; primary immunodeficiency; Lymphocytic Choriomeningitis Virus; autoimmune disease
Fässler Mirjam, Diem Stefan, Mangana Joanna, Hasan Ali Omar, Berner Fiamma, Bomze David, Ring Sandra, Niederer Rebekka, del Carmen Gil Cruz Cristina, Pérez Shibayama Christian Ivan, Krolik Michal, Siano Marco, Joerger Markus, Recher Mike, Risch Lorenz, Güsewell Sabine, Risch Martin, Speiser Daniel E., Ludewig Burkhard, Levesque Mitchell P., Dummer Reinhard, Flatz Lukas (2019), Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients, in Journal for ImmunoTherapy of Cancer
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Diem Stefan, Fässler Mirjam, Bomze David, Ali Omar Hasan, Berner Fiamma, Niederer Rebekka, Hillmann Dorothea, Mangana Joanna, Levesque Mitchell P., Dummer Reinhard, Risch Lorenz, Recher Mike, Risch Martin, Flatz Lukas (2019), Immunoglobulin G and Subclasses as Potential Biomarkers in Metastatic Melanoma Patients Starting Checkpoint Inhibitor Treatment, in Journal of Immunotherapy
Quteineh Lina, Wójtowicz Agnieszka, Bochud Pierre-Yves, Crettol Severine, Vandenberghe Frederik, Venetz Jean-Pierre, Manuel Oriol, Golshayan Dela, Lehmann Roger, Mueller Nicolas J., Binet Isabelle, van Delden Christian, Steiger Jürg, Mohacsi Paul, Dufour Jean-Francois, Soccal Paola M., Kutalik Zoltan, Marques-Vidal Pedro, Vollenweider Peter, Recher Mike, Hess Christoph, Pascual Manuel, Eap Chin B. (2019), Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients, in American Journal of Transplantation
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Recher Mike, Hirsiger Julia R., Bigler Marc B., Iff Martin, Lemaître Barbara, Scherer Kathrin, Häusermann Peter, Siegrist Claire-Anne, Berger Christoph T. (2018), Immune system correlates of extensive limb swelling in response to conjugated pneumococcal vaccination, in npj Vaccines
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Schwab Charlotte, Gabrysch Annemarie, Olbrich Peter, Patiño Virginia, Warnatz Klaus, Wolff Daniel, Hoshino Akihiro, Kobayashi Masao, Imai Kohsuke, Takagi Masatoshi, Dybedal Ingunn, Haddock Jamanda A., Sansom David M., Lucena Jose M., Seidl Maximilian, Schmitt-Graeff Annette, Reiser Veronika, Emmerich Florian, Frede Natalie, Bulashevska Alla, Salzer Ulrich, Schubert Desirée, Hayakawa Seiichi, Okada Satoshi, et al. (2018), Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4–insufficient subjects, in Journal of Allergy and Clinical Immunology
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Imfeld Stephan, Rottenburger Christof, Schegk Elke, Aschwanden Markus, Juengling Freimut, Staub Daniel, Recher Mike, Kyburz Diego, Berger Christoph T, Daikeler Thomas (2018), [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
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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
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Primary immunodeficiencies (PID) comprise more than 300 different disorders that affect the development, function -or both- of the immune system due to mutations in immune-related genes. During the past few years evidence has accumulated indicating that PID, besides their association with infection, are also associated with autoimmunity and immune-dysregulation, probably due to the impaired immune-tolerance. PID patients that suffer from non-infectious complications such as autoimmunity or immune-dysregulation have an increased mortality when compared to PID patients with only infectious complications. Since PID are monogenic diseases, PID-patients with autoimmunity, or relevant mouse models, represent a valuable tool to understand general mechanisms involved in the induction of autoimmunity and immune dysregulation. It has been recently demonstrated that alterations in the same PID gene may lead to different clinical entities depending on the functional severity of the mutation. This is exemplarily demonstrated in PID associated with mutations in the recombination activating genes RAG1 and RAG2 that might lead to various clinical phenotypes ranging from severe combined immunodeficiency to late-onset autoimmunity.In this proposal, we aim to analyze molecular mechanisms involved in the generation PID-associated immune-dysregulation and autoimmunity. We will do this by analyzing mouse models with a gradual decrease of RAG function due to complete loss-of function- or hypomorphic mutations in the RAG gene locus. These mouse models with RAG function ranging from normal down to complete loss of function will be infected with a persistence-prone virus (Lymphocytic Choriomeningitis Virus (LCMV) and the formation of anti-viral and autoimmune T and B cell responses will be monitored.