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.
- HELICAL - HEalth data LInkage for ClinicAL benefit (2018)
Source of Funding: EU, Horizon 2020 / MSCA / ITN
- ACKITEC: From AAV to Chronic KIdney disease: contribution of TEnascin-C (2016)
Source of Funding: FWF (Austrian Science Fund), I 2974 International Projects
- RELENT - RELapses prevENTion in chronic autoimmune disease: common mechanisms and co-morbidities (2015)
Source of Funding: EU, H2020-PHC-2015
Coordinator of the collaborative project
- INTRICATE - Infectious triggers of chronic autoimmunity (2010)
Source of Funding: EU, FP7-HEALTH-2010
Coordinator of the collaborative project
- Leone, D.A. et al., 2017. Surface LAMP-2 Is an Endocytic Receptor That Diverts Antigen Internalized by Human Dendritic Cells into Highly Immunogenic Exosomes. The Journal of Immunology, 199(2), pp.531-546. Available at: http://dx.doi.org/10.4049/jimmunol.1601263.
- Hubert, V. et al., 2016. LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes. Biology Open, 5(10), pp.1516-1529. Available at: http://dx.doi.org/10.1242/bio.018648.
- Leone, D.A. et al., 2016. The Phenotypic Characterization of the Human Renal Mononuclear Phagocytes Reveal a Co-Ordinated Response to Injury A. Haziot, ed. PLOS ONE, 11(3), p.e0151674. Available at: http://dx.doi.org/10.1371/journal.pone.0151674.
- Peschel, A. et al., 2013. Autoantibodies to hLAMP-2 in ANCA-Negative Pauci-Immune Focal Necrotizing GN. Journal of the American Society of Nephrology, 25(3), pp.455-463. Available at: http://dx.doi.org/10.1681/ASN.2013030320.
- Grigorieva, I.V. et al., 2019. A Novel Role for GATA3 in Mesangial Cells in Glomerular Development and Injury. Journal of the American Society of Nephrology, 30(9), pp.1641–1658. Available at: http://dx.doi.org/10.1681/ASN.2018111143.