immune-dysregulation; immunodeficiency; SP110; RAG; antibody-deficiency; autoimmunity
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
, 7(1), 50-50.
Delmonte Ottavia M., Baldin Fabian, Ovchinsky Nadia, Marquardsen Florian, Recher Mike, Notarangelo Luigi D., Kosinski Slawomir M. (2019), Novel Missense Mutation inSP110Associated with Combined Immunodeficiency and Advanced Liver Disease Without VOD, in Journal of Clinical Immunology
Burgener Anne-Valérie, Bantug Glenn R., Meyer Benedikt J., Higgins Rebecca, Ghosh Adhideb, Bignucolo Olivier, Ma Eric H., Loeliger Jordan, Unterstab Gunhild, Geigges Marco, Steiner Rebekah, Enamorado Michel, Ivanek Robert, Hunziker Danielle, Schmidt Alexander, Müller-Durovic Bojana, Grählert Jasmin, Epple Raja, Dimeloe Sarah, Lötscher Jonas, Sauder Ursula, Ebnöther Monika, Burger Bettina, Heijnen Ingmar, et al. (2019), SDHA gain-of-function engages inflammatory mitochondrial retrograde signaling via KEAP1–Nrf2, in Nature Immunology
, 20(10), 1311-1321.
Hirsiger Julia R, Fuchs Philipp S, Häusermann Peter, Müller-Durovic Bojana, Daikeler Thomas, Recher Mike, Hirsch Hans H, Terracciano Luigi, Berger Christoph T (2019), Syphilis Reactivates Latent Epstein-Barr Virus Reservoir via Toll-Like Receptor 2 and B-Cell Receptor Activation, in Open Forum Infectious Diseases
, 6(9), 1-6.
Berner Fiamma, Bomze David, Diem Stefan, Ali Omar Hasan, Fässler Mirjam, Ring Sandra, Niederer Rebekka, Ackermann Christoph J., Baumgaertner Petra, Pikor Natalia, Cruz Cristina Gil, van de Veen Willem, Akdis Mübeccel, Nikolaev Sergey, Läubli Heinz, Zippelius Alfred, Hartmann Fabienne, Cheng Hung-Wei, Hönger Gideon, Recher Mike, Goldman Jonathan, Cozzio Antonio, Früh Martin, Neefjes Jacques, et al. (2019), Association of Checkpoint Inhibitor–Induced Toxic Effects With Shared Cancer and Tissue Antigens in Non–Small Cell Lung Cancer, in JAMA Oncology
, 5(7), 1043-1043.
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, 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
, 19(1), 238-246.
Berger Christoph T, Rebholz-Chaves Birke, Recher Mike, Manigold Tobias, Daikeler Thomas (2019), Serial IL-6 measurements in patients with tocilizumab-treated large-vessel vasculitis detect infections and may predict early relapses, in Annals of the Rheumatic Diseases
, 78(7), 1012-1014.
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
, 42(3), 89-93.
Primary immunodeficiencies (PID) comprise more than 350 different clinical entities 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, probably due to the impaired immune-tolerance.PID related autoimmunity is strongly linked to clinical complications and increased mortality. 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 different mutations in the same PID gene may lead to different clinical entities depending on the functional impact 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 further 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 RAG1 and RAG2 genes.In addition, as suggested by the mid-term SNF review, we will further characterize the function of SP110, another PID-gene that is associated with severe immunopathology and mortality following pneumocystis infection. This will be done by comparing the function of SP110 competent vs. deficient human T cells.In summary, the work proposed here might help to understand mechanisms involved in the development of immune-dysregulation, immunopathology and autoimmunity in patients with primary immunodeficiencies.