So aHUS is an autoimmune disease?
Well actually not but depending on the definition of aHUS there can be an autoimmune like element.
Why so equivocal?
Because autoimmunity needs to be understood.
What’s to understand?
A lot. Firstly an autoimmune disease is a condition arising from an abnormal immune response to a normal body part in which the body attacks and damages its own tissues,
Give an example.
GPA, Granulated Polyangititis. It is disease in which the body attacks its healthy blood vessels affecting the kidneys and lung tissues.
Sounds like aHUS to me.
Hold on. So when an intruder invades our body our immune system protects us by identifying and eliminating the intruder/ attacker.
I know that.
But if the immune system itself makes something that can actually end up attacking its own healthy cells that’s an autoimmune disease.
Sounds like aHUS even more, so is complement involved in GPA?
GPA patients appear to have elevated complement and there may be complement involvement too . But that is not what causes it. It is caused antibodies, something created by the immune system and they are called antineutrophil cytoplasmic antibodies. It is an ANCA associated vasculitis. Although it follows a very complex process in essence the autoantibodies destroys neutrophils, which are white blood cells, a part of the innate immune system, and they release an excessive inflammation stimulating response.
In GPA case an excessive inflammatory response can involve that other bit of C5, i.e. “C5a”. Not C5b as in aHUS. Part of the treatment of PGA is the C5a blocker Avacopan. It is a monoclonal antibody like eculizumab.
So like aHUS?
Recorded incidences of autoimmune diseases have increased over the last 40 years. Future predictions indicate that these diseases will affect between 15 and 20% of the world’s population. Mostly women so not rare overall but some like PGA are very rare.
I get it aHUS is rare too.
Diagnosis of autoimmune diseases is made with blood tests which reveal the autoantibodies.
Like the parts of the complement system?
No they are not autoantibodies. They are proteins.
But defects in them are associated with uncontrolled complement and over reaction where complement damages parts of the body.
Yes but they are not autoantibodies so what is happening is not an autoimmune disease. aHUS is not an autoimmune disease
Wait what!? Something has struck me!
Anti Factor H autoantibodies?
Yes you said that at the beginning that a bit of aHUS is an autoimmune disease like?
Yes the clue is in the name Anti Factor H Autoantibodies
I have heard of them some people have them and get aHUS
A lot of people have them and don’t get aHUS either.
So why do people have them and why are they anti FH.
Difficult to explain why people have them which is the same for all autoantibodies created by the immune system for autoimmune diseases. There are Anti Factor I autoantibodies bodies too but you probably have not heard of them.
But when it comes Complement Factor H the auto antibodies attach to parts of the FH protein and then what was a perfectly working CFH before becomes hampered from doing its job of controlling complement.
That is different, yet the same.
Yes but get rid of the anti FH autoantibodies and complement can work normally again and this version of aHUS is “cured”. But in aHUS with defective factor H it can only be got rid of temporarily by changing the patient’s plasma but new defective factor H is produced by the body once more. The patient really needs a complement inhibitor.
Why do people get autoantibodies how are they got rid of?
As said earlier no one really knows why but there are lot of them and mostly they are not a health problem. There is a suggestion that they are created when the adaptive immune system is under stress, e.g. healthy GPA patients who have had COVID 19 may acquire ANCA.
Autoimmune diseases are treated by immunosuppression. The patient therefore is more exposed to infection. GPA is treated this way.
So either way the immune system is suppressed but just different parts of it. Complement for aHUS , another part of immune system for autoimmune diseases.
Yes.
So is Anti Factor H Autoantibody aHUS a disease within a disease or its own autoimmune disease?
It is aHUS but which is “autoimmune like”. We will know better if and when aHUS is ever renamed and redefined.
So will the other true autoimmune diseases currently embraced by the confusing “secondary aHUS” tag but which are not aHUS.
Article No: 749
