Immune dysregulation in patients with vasculitis
Research type
Research Study
Full title
Immune dysregulation in patients with vasculitis and the role of immune checkpoints in disease pathogenesis of primary vasculitides
IRAS ID
249794
Contact name
David Jayne
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge
Duration of Study in the UK
0 years, 6 months, 3 days
Research summary
Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), a rare autoimmune disease causing
inflammation of blood vessels can affect different organs (such as kidneys, lungs) leading to organ failure. An imbalance between activators and regulators of the immune system leads to the development of white blood cells that attack self (such cells are called auto-reactive lymphocytes).Studies from the field of cancer showed that a specific pathway called immune checkpoint pathway is important in the regulation of the immune system. A protein called PD-1 that is expressed on T lymphocytes (a subset of lymphocytes) interacts with a complementary protein called PD-L1 that is expressed on a wide variety of cells. When PD-1 is engaged by PD-L1, T cells are inhibited and the immune system is regulated. PD-1 was also shown to be present on hyper-activated T lymphocytes.
In some forms of cancers, the tumor expresses significant amounts of PD-L1 thereby deactivating the T lymphocytes, thus escaping from the immune system. New therapies that block PD-1 or PD-L1 were successful in treating some cancers. However, because of T cell hyper-activation, some patients were reported to develop auto-immune diseases such as vasculitis, thereby suggesting a role for this system in vasculitis.
We hypothesise that patients with vasculitis have low levels of the immune system regulators (i.e. low level of PD-L1) and have excessive levels of activated T lymphocytes expressing PD-1. We propose to test this hypothesis by studying the tissue/cells from inflamed sites (kidney and lungs) obtained for routine clinical purposes from patients with AAV and compare it to tissue obtained from control conditions. Historical (where prior consent available) and prospective samples will be used in this study. All prospective samples from kidney biopsy and broncho-alveolar lavage (fluid obtained from the washing of lungs done for clinical diagnostic purposes) procedures will be obtained after appropriate consent.
REC name
Wales REC 7
REC reference
19/WA/0041
Date of REC Opinion
6 Feb 2019
REC opinion
Favourable Opinion