Detail

Keywords

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

Research group(s)

• Renal Pathology and Immunopathology
  Head: Renate Kain
  Research Area: Pathogenesis of ANCA associated autoimmune vasculitis (AAV) Autoantibodies to human lysosomal membrane protein-2 (hLAMP-2) and other glyocoproteins in AAV Autoimmunity to membrane proteins in the pathogenesis of FNGN and AAV The role of extracellular vesicles as biomarkers in AAV The role of autophagy in antigen presentation and autoimmunity
  Members:
  Virginie Hubert
  Renate Kain

Research interests

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.

Grants

• Bigpicture - A central repository of digital pathology slides to boost the development of artificial intelligence (2021)
  Source of Funding: EU, Innovative Medicines Initiative 2
  Principal Investigator
• HELICAL - HEalth data LInkage for ClinicAL benefit (2018)
  Source of Funding: EU, Horizon 2020 / MSCA / ITN
  Principal Investigator
• ACKITEC: From AAV to Chronic KIdney disease: contribution of TEnascin-C (2016)
  Source of Funding: FWF (Austrian Science Fund), I 2974 International Projects
  Principal Investigator
• 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

Selected publications

1. Oszwald, A. et al. (2022) ‘Digital Spatial Profiling of Glomerular Gene Expression in Pauci-Immune Focal Necrotizing Glomerulonephritis’, Kidney360, 4(1), pp. 83–91. Available at: http://dx.doi.org/10.34067/kid.000461202.
2. Fayçal, C.A. et al. (2022) ‘An adapted passive model of anti-MPO dependent crescentic glomerulonephritis reveals matrix dysregulation and is amenable to modulation by CXCR4 inhibition’, Matrix Biology, 106, pp. 12–33. Available at: http://dx.doi.org/10.1016/j.matbio.2022.01.001.
3. Hubert, V. et al. (2022) ‘Modulating Chaperone-Mediated Autophagy and Its Clinical Applications in Cancer’, Cells, 11(16), p. 2562. Available at: http://dx.doi.org/10.3390/cells11162562.
4. Małys, M.S. et al. (2021) ‘Isolation of Small Extracellular Vesicles from Human Sera’, International Journal of Molecular Sciences, 22(9), p. 4653. Available at: http://dx.doi.org/10.3390/ijms22094653.
5. Kitching, A.R. et al. (2020) ‘ANCA-associated vasculitis’, Nature Reviews Disease Primers, 6(1). Available at: http://dx.doi.org/10.1038/s41572-020-0204-y.