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
, 3(1), 17-17.
Bischof Antje, Manigold Tobias, Barro Christian, Heijnen Ingmar, Berger Christoph T, Derfuss Tobias, Kuhle Jens, Daikeler Thomas (2018), Serum neurofilament light chain: a biomarker of neuronal injury in vasculitic neuropathy, in Annals of the Rheumatic Diseases
, 77(7), 1093-1094.
Frick Corina, Dettinger Philip, Renkawitz Jörg, Jauch Annaïse, Berger Christoph T., Recher Mike, Schroeder Timm, Mehling Matthias (2018), Nano-scale microfluidics to study 3D chemotaxis at the single cell level, in PLOS ONE
, 13(6), e0198330-e0198330.
Miho Enkelejda, Yermanos Alexander, Weber Cédric R., Berger Christoph T., Reddy Sai T., Greiff Victor (2018), Computational Strategies for Dissecting the High-Dimensional Complexity of Adaptive Immune Repertoires, in Frontiers in Immunology
, 9, 224.
Berger Christoph T, Recher Mike, Daikeler Thomas (2018), Interleukin-6 flags infection in tocilizumab-treated giant cell arteritis, in Rheumatology
, 57(1), 196-197.
Imfeld Stephan, Rottenburger Christof, Schegk Elke, Aschwanden Markus, Juengling Freimut, Staub Daniel, Recher Mike, Kyburz Diego, Berger Christoph T, Daikeler Thomas (2017), [ 18 F]FDG positron emission tomography in patients presenting with suspicion of giant cell arteritis—lessons from a vasculitis clinic, in European Heart Journal - Cardiovascular Imaging
Ankli B, Kyburz D, Hirschmann A, Hügle T, Manigold T, Berger CT, Daikeler T (2017), Calcium pyrophosphate deposition disease: a frequent finding in patients with long-standing erosive gout, in Scandinavian Journal of Rheumatology
, 47(2), 127-130.
The adaptive immune system protects us from infections and cancer. T cells and antibodies, which are produced by B cells, recognize specific motifs on proteins, so-called epitopes presented on their surface. Failure of the immune system to distinguishing self from non-self proteins can result in autoimmune disease. An integrative model suggests that this can occur in genetically predisposed subjects on the basis of systemic immune dysregulation supporting subsequent expansion of auto-reactive cells . Auto-immune vasculitis syndromes comprise a spectrum of diseases defined by primary inflammation of blood vessels, with Giant cell arteritis (GCA) being the most frequent form . GCA manifests with constitutional symptoms, headache, and a systemic inflammatory syndrome, and patients are at risk for feared ischemic complications such as vision loss or stroke . Studies on the immunopathology revealed that in GCA, CD4 T cells and macrophages are the key effector cells mediating vascular destruction in inflamed blood vessels . The chain of events leading to GCA, including the immunological target of autoreactive T cells remains, however, unknown. While it is generally assumed that T cells recognize self-proteins from the vessel wall, very recently, a potential link between GCA and the presence of Varicella Zoster virus (VZV) in the arteries has been reported [3-5]. This suggests that VZV might trigger autoimmunity or could be the immunological target itself. A better understanding of the adaptive immune response in GCA has the potential to provide a rational for novel treatment strategies (e.g. addition of antiviral therapy) and/or to uncover individualized disease activity biomarkers (e.g. abundance of antigen specific T cell clones in the blood). To address unmet needs in GCA, we established a prospective cohort at the University Hospital Basel (Basler Riesenzellarteritis Kohorte; BARK) [6-8]. We collect clinical data and biological samples from patients and disease controls, the latter mostly being patients with initially suspected GCA. Taking advantage of this cohort and our expertise in T cell immunology and epitope discovery [9-11] the General Aim of this prolongation proposal is to complete our studies on the expansion of antigen-specific effector T cells in GCA, and their potential use as tool to better diagnose or stratify patients.Specific Aim #1: Screening for- and characterizing pathogenic T cells in GCA. Stimulating peripheral blood T cells using (i) protein fractions extracted from aortic tissue or (ii) VZV antigen, will allow testing whether reactive T cells can be detected in the blood using IFN-? ELISpot and flow cytometry based assays. Antigen specific T cell lines targeting VZV or blood vessel proteins will be generated that can be employed in subsequent antigen characterization assays and be used for T cell receptor (TCR) sequencing. This may provide arguments for a self- or pathogen-derived target epitope and could thereby help unravel the nature of the immune response attacking the arteries.Specific Aim #2: Assessing whether T cell clones in the inflammatory lesions of GCA biopsies share a TCR repertoire, and test their potential as biomarkers. Laser micro-dissection, and a multiplex PCR approach for the analysis of the TCR repertoire in the inflamed artery will be employed to test for the existence of dominant or public T cell clones. This would provide evidence for an antigen specific immune response in GCA. Quantitative PCR will then be used to track GCA-specific T cell clones (as identified in Specific Aim #1 or 2) longitudinally in the peripheral blood. By correlating clonal frequencies with disease activity, their relevance in disease pathogenesis can be assigned, and their value to serve as biomarker for immunosuppressive treatment-stewardship defined.