Allergy and Immunology; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Autoantibodies; Autoimmune Diseases; Autophagy; Cell Biology; Exosomes; Genomics; Lysosomal-Associated Membrane Protein 2; Microbiology; Microscopy; Microscopy, Confocal; Microscopy, Electron, Transmission; Microscopy, Immunoelectron; Nephrology; Pathology; Proteomics
The central theme of my research is to elucidate pathogenic disease mechanisms by combining the insights derived from morphological examination of injured tissues with advanced molecular techniques. The ultimate goal is to clarify mechanisms of autoimmunity and develop more effective therapies using ANCA associated vasculitis (AAV) as a model. Our laboratory made the original discovery of autoantibodies to human lysosomal membrane protein-2 (hLAMP-2) in patients with AAV and further detailed characterisation showed they are highly prevalent and correlate with disease activity. Crossreactivity of human anti-LAMP-2 antibodies with antibodies to FimH and experimental data provided evidence for FimH triggered autoimmunity to LAMP-2 as novel pathogenetic mechanism in AAV. Follow up studies confirmed the presence of anti-LAMP-2 autoantibodies also in ANCA negative patients and detailed characterisation revealed direct binding of the autoantiantibodies to glomerular endothelium. This highlighted the necessity of a better understanding about their interactions with cells and has become a critical part of our research program on the effects of anti-LAMP-2 antibodies on LAMP-2's normal function.
The clinical aspects of autoimmunity to LAMP-2 are currently followed up in international collaborations that will determine whether anti-hLAMP-2 autoantibodies can be used as a biomarker that faithfully predicts disease activity.
Techniques, methods & infrastructure
We use tissue samples from human and rodent models complemented by information gained from serum, plasma, DNA and clinical data. Our techniques extend from classical histology to immunomorphological methods in light and electron microscopy and include application of immunological methods, culture of primary cells and cell lines, analysis of DNA and RNA from cells, human and animal tissues, classical and advanced cloning techniques to generate techniques with the intent of generating transformed cell lines and transgenic models as tools necessary in our research programme.