Research update – from Spring Newsletter 2016

This week’s Blog is an article from our Spring Newsletter by PhD student Catriona Walls.  LCTF help fund this research at The University of Aberdeen.

Research at The University of Aberdeen is well and truly underway, now in its third year.  Our initial aim was to create a system where we would be able to study live immune cells from patients who suffer from ANCA-associated vasculitides (AAV), these include Microscopic Polyangiitis (MPA), Eosinophilic Granulomatosis Polyangiitis (EGPA, or Churg-Strauss) and Granulomatosis Polyangiitis (GPA, or Wegeners).

In healthy individuals, antibodies are produced in response to infection and serve to protect that person the next time they encounter that same infection.  These antibodies will stimulate immune cells to mount a response against whatever pathogen has entered the body, usually eradicating the problem swiftly and without too many problems.  Patients with AAV produce antibodies and inappropriately stimulate immune cells to ‘attack’ blood vessels.  Blood vessels are required to deliver oxygen to all organs in the body and so any damage can affect these organs and that is why we see such devastating symptoms in Vasculitis.

The system we have developed essentially mimics what we believe to be the key players in damaging the blood vessels.  By taking the live immune cells from patients we can see how these cells behave in a 4D environment and discover whether they are different from a patient who has been newly diagnosed vs entering remission or relapsing etc.  Being able to distinguish between stages of disease means that doctors who treat patients can alter medication to potentially prevent a relapse from occurring or reduce side effects of such medication.

There are several different immune cells behaviours that we are interested in.  These include:

Degranulation – the release of toxic enzymes from white blood cells, usually after interaction with ANCA.

Migration – how quick and far a white blood cell moves on the surface of the blood vessel lining cells?

Transmigration – do the white blood cells move through the blood vessel lining and which way do they go, for example directly through the middle of the cell or in between two cells?

Particle uptake – how much of the white blood cell contents can be seen inside the blood vessel lining cells?

Serum analysis – We want to know levels of cytokines and chemokines (chemicals which allow cells to communicate with each other) in the blood of patients and healthy donors.

This image shows a monocyte (white blood cell) in the process of degranulation. Notice the small granules – these contain enzymes which degrade and damage the blood vessels.

We have seen differences already between the behaviour of immune cells from patients compared to healthy donors.  The immune cells from patients are more active in all the parameters we analyse, which is what we would expect to see.  This is great news as it means that the system we have developed does the job we want it to.  The next step is to repeat the samples from our current patients.  This will give us a comparison against different disease stages from the same patient and allow us to build up a profile of immune cell behaviour.

There has been a great response from patients at the clinic and on the ward who are willing to donate their blood to help in our research.  Without their participation we would be unable to do any of this work so thank you for getting involved.

 

Related link:

Funding for student and research into rare disease