World Kidney Day: researchers investigate rare autoimmune disease, AAV
Posted on: 10 March 2022
Researchers at The Trinity Health Kidney Centre, based in the Trinity Translational Medicine Institute in Trinity College have previously shown that, in addition to normal neutrophils (the most abundant immune cells in our body), a subclass of neutrophils – called ‘low density granulocytes/neutrophils’ – is increased in patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (AAV), a rare, severe small vessel vasculitis that affects multiple organs and has a high acute mortality risk. This increase also relates to how severe the disease is.
Researchers however, do yet not understand whether these neutrophils are directly causing AAV or whether they increase in response to inflammation. Interestingly, they are also found in other disease conditions such as COVID-19, cancer and sepsis, but remain poorly defined.
To coincide with World Kidney Day, we highlight the work of PhD researcher Amrita Dwivedi (pictured) from the Trinity Health Kidney Centre which aims to understand the possible role of these low-density neutrophils in AAV pathogenesis.
Small vessel vasculitis
Neutrophils are the most abundant immune cells in our body and play an important role in defence against infections and other threats. Defects in neutrophil function can have severe consequences and lead to various diseases. One such disease is Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (AAV), also known as ‘small vessel vasculitis’.
There are two types of small vessel vasculitis: Wegeners’ Granulomatosis (GPA) and Microcropic polyangiitis (MPA).
Both types are characterised by antibodies that target the body’s own neutrophil proteins causing defective neutrophil function. Although rare, AVV can result in organ damage and failure, with the kidney and lung as major targets. As many as a quarter of AAV patients who require renal replacement therapy (kidney dialysis) at the time of diagnosis die within six months of diagnosis, and one in three patients never regain kidney function.
Neutrophils were traditionally thought to be a uniform cell type with a well-defined role in the immune system, however, it is now thought that neutrophils are made up of several subclasses with specialised function which either resolve or worsen inflammation.
Research Impact
Amrita’s research aims is to understand the role played by low-density neutrophils in the immunopathology of AAV, and how their role differs in other inflammatory diseases (such as COVID-19, cancer and sepsis). This research has found that low-density neutrophils are aberrantly activated in AAV patients. These neutrophils actively produce the proteins that are targeted by ANCA antibodies and have been shown to readily damage the small vessels – suggesting that low-density neutrophils may play a key role in kidney and lung damage.
Amrita said:
I hope that my findings will broaden our understanding of the immunopathogenesis of AAV and will inform future studies which aim to identify potential therapeutic targets in patients with AAV. I believe that basic scientific research is the foundation of any medical advancement.
Amrita is supervised by Professor/Consultant of Nephrology, Professor Mark Little of the Trinity Health Kidney Centre and Dr Ronan Desmond, Consultant Haematologist at Tallaght University Hospital, and is funded by the Irish Research Council.
To learn more about the Trinity Health Kidney Centre, visit: https://www.tcd.ie/medicine/thkc/
To learn more about World Kidney Day, visit here