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Kain Group

Research Focus

ANCA associated vasculitis (AAV) is an acute inflammatory disease leading to rapid and irreversible kidney failure. It is associated with antibodies against neutrophil cytoplasmic antigens (ANCA) such as myeloperoxidase, proteinase-3, or the lysosome-associated membrane protein-2 (LAMP-2), more recently identified (Kain et al., 1995). Further characterization reveals that LAMP-2 antibodies are highly prevalent in AAV patients and directly correlated with disease activity (Kain et al., 2008). Moreover, they are also found in ANCA negative patients where they bind to the glomerular endothelium (Peschel et al., 2014). These antibodies commonly recognized two main epitopes, one of them sharing 100% homology with the bacterial adhesion protein FimH whose ability to trigger immunity to LAMP-2 constitutes a novel pathogenic mechanism in AAV. This highlights the need for a better understanding of the functions associated with LAMP-2 as well as their potential disruption due to autoantibodies and the extent to which they are contributing to the pathogenicity of vasculitis.

Main Objectives

The main goal of the laboratory is to elucidate the pathological mechanisms involved in the development and progression of ANCA associated vasculitis (AAV). For this purpose, we are aiming to identify or validate potential markers of AAV and to investigate their potential to predict response to treatment as well as disease outcome and progression.

Content Research

The laboratory expertise relies on a broad range of methodologies required for cellular and molecular biology including cell culture, confocal and electron microscopy, immunological methods, DNA and RNA analysis as well as classical and advanced cloning methods aiming to generate transform cell lines or transgenic models as tools necessary in our research program.

To apply these methods we are using samples (tissue, serum, DNA) from rodent models and human as well as in vitro models including the culture of induced pluripotent stem cells (iPSC).

Exosome as a biomarker for ANCA associated vasculitis

Exosomes are extracellular vesicles formed in late endosomes and release into the surrounding medium where they play a critical role in intercellular communication. Exosomes are relatively uniform, but their cargo is highly dependent on the originating cell and their activation status. Accordingly, exosomes purified from the blood of individuals with inflammatory diseases are potential biomarkers that could provide insights into pathogenesis and disease activity. The purpose of this project is to analyze the surface protein pattern on exosomes to determine the quiescent and active stage of ANCA Associated Vasculitis and predict the probability of relapses.

Exosomes are extracellular vesicles formed in late endosomes and release into the surrounding medium where they play a critical role in intercellular communication. Exosomes are relatively uniform, but their cargo is highly dependent on the originating ce

The importance of LAMP-2 in different forms of autophagy namely chaperone-mediated autophagy (CMA)(Cuervo & Dice, 1996) and macroautophagy (Hubert et al., 2016) has been firmly established and constitutes one the research topics of the laboratory. For this purpose, we are working in collaboration with a German biotech company on the development and validation of specific modulators of CMA. Besides we are also working on the identification of genetic variants associated with the development of drug-induced phospholipidosis, a pathology characterized by the accumulation of lamellar bodies within the lysosomes.

Using iPSC to investigate the pathophysiological mechanism of ANCA associated vasculitis

This project aims to establish a disease cellular model using induced pluripotent stem cells (iPSCs) derived from patients with recurring or transient anti-neutrophil cytoplasmic (ANCA) associated vasculitis. IPSCs are differentiated into various immune cells (monocytes, dendritic cells, macrophages) and used to investigate antigen presentation. This allows us to analyse individual variations within patients (cell behavior, genetic variants) which potentially results in different disease outcomes or treatment responses. Ultimately this should allow us to provide personalized treatment adapted to each patient's needs.

KAIN, Renate Univ.Prof.in Dr.in PhD

Head of Department

T: +43 (0) 40400 - 36500
F: +43 (0) 40400 - 37070
E: renate.kain@meduniwien.ac.at

» Researcher Profile
» ORCID

HUBERT, Virginie, PhD MSc

KALTENECKER, Christopher Ing. PhD

NACKENHORST, Maja Dr.in

OSZWALD, Andre Dr.

  • Grigorieva, I. V., Oszwald, A., Grigorieva, E. F., Schachner, H., Neudert, B., Ostendorf, T., Floege, J., Lindenmeyer, M.J., Cohen, C.D., Panzer, U., Aigner, C., Schmidt, A., Grosveld, F., Thakker R.V., Rees, A.J. & Kain, R. (2019). A novel role for GATA3 in mesangial cells in glomerular development and injury. Journal of the American Society of Nephrology, 30(9), 1641–1658. https://doi.org/10.1681/ASN.2018111143
  • Leone, D. A., Peschel, A., Brown, M., Schachner, H., Ball, M. J., Gyuraszova, M., Salzer-Muhar, U., Fukuda, M., Vizzardelli C., Bohle, B., Rees, A.J. & Kain, R. (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), 531–546. https://doi.org/10.4049/jimmunol.1601263
  • Hubert, V., Peschel, A., Langer, B., Gröger, M., Rees, A., & Kain, R. (2016). LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes. Biology Open, 5(10), 1516–1529. https://doi.org/10.1242/bio.018648
  • Peschel, A., Basu, N., Benharkou, A., Brandes, R., Brown, M., Dieckmann, R., Rees, A.J. & Kain, R. (2014). Autoantibodies to hLAMP-2 in ANCA-negative pauci-immune focal necrotizing GN. Journal of the American Society of Nephrology, 25(3), 455–463. https://doi.org/10.1681/ASN.2013030320
  • Kain, R., Exner, M., Brandes, R., Ziebermayr, R., Cunningham, D., Alderson, C. A., Davodovits, A., Raab, I., Jahn, R., Ashour, O., Spitzsauer, S., Sunder-Plassmann, G., Fukuda, M., Klemm, P., Rees, A.J. &Kerjaschki, D. (2008). Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nature Medicine, 14(10), 1088–1096. https://doi.org/10.1038/nm.1874

The Kain group is funded by the EU, Horizon 2020 / MSCA / ITN:

Project: “HELICAL" - HEalth data LInkage for ClinicAL benefit (2019-2022)

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The Kain group was funded by the FWF (Austrian Science Fund), I 2974 International Projects

Project: ACKITEC: From AAV to Chronic KIdney disease: contribution of TEnascin-C (2016)

The Kain group was funded by the EU, H2020-PHC-2015

Project: RELENT - RELapses prevENTion in chronic autoimmune disease: common mechanisms and co-morbidities (2015)

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The Kain group was funded by the EU, FP7-HEALTH-2010

Project: INTRICATE - Infectious triggers of chronic autoimmunity (2010)

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KAIN, Renate Univ.Prof.in Dr.in PhD

Head of Department

T: +43 (0) 40400 - 36500
F: +43 (0) 40400 - 37070
E: renate.kain@meduniwien.ac.at

» Researcher Profile
» ORCID