How Microclots cause Autoantibodies in Long Covid
...and the autoimmune-type symptoms in patients
We have seen over the past few months that microclots are the major cause of many of the symptoms of Long Covid.
Microclots are the likely cause of the debilitating fatigue seen in Long Covid.
Microclots are potentially responsible for many of the circulatory and cardiac symptoms experienced in Long Covid, including POTS.
Microclots are potentially responsible for the brain fog and other neurological effects seen in Long Covid as well.
And as we have examined over the past several months, the microclots in Long Covid are the result of improper folding of fibrinogen and the polymerization of that mis-folded fibrinogen into amyloids - what I have taken to calling abnormal amyloids of fibrinogen.
And in Long Covid, these microclots are induced and catalyzed by the Covid spike protein.
Today I want to talk about how microclots, these abnormal amyloids of fibrinogen, can cause the generation of autoantibodies in Long Covid.
There is currently a lot of discussion about autoantibodies observed in Long Covid and the autoimmune-type reactions that these autoantibodies cause in Long Covid patients.
Autoantibodies are causing a lot of suffering in Long Covid patients. But the specific autoimmune reactions (and therefore the autoantibodies generated), seems to vary widely from person to person.
How can one disease like Long Covid cause so many different types of autoimmune responses and generate so many different autoantibodies?
And how can one mechanism explain and account for many (or all) of them?
To answer these questions, we first have to review how (and why) antibodies are generated under normal conditions. Then we can examine how microclots in Long Covid can generate autoantibodies.
How & why do we make antibodies under normal conditions?
The normal function of antibodies is to detect foreign proteins and biomolecules. This is a defensive mechanism to protect us from pathogens like bacteria and viruses, as well as any other type of foreign proteins that might somehow make their way into our bodies.
Under normal healthy conditions, our own proteins and biomolecules do NOT cause antibodies to be generated.
Our immune systems are very finely tuned to be able to discriminate between our ‘self’ and foreign ‘non-self’ proteins that might be dangerous.
This specificity is achieved by antibodies recognizing specific sequences of amino acids in proteins, usually anywhere from 5-10 amino acids long. These specific amino acid sequences that are recognized by an antibody are called epitopes.
Now, our bodies make antibodies all the time that fight off infections but don’t attack our own body.
How does that work?
Typically when an antibody is raised against a foreign protein, the epitope that’s detected is unique to the foreign protein and is not an amino acid sequence that we have in one of our proteins.
This allows the antibody that’s created to bind to that epitope in the foreign protein and mark the protein for destruction, without affecting any of our own natural proteins.
This is the way the immune system is supposed to work.
How are Autoantibodies Generated?
So what goes wrong in the immune system when autoantibodies are generated and we have autoimmune diseases?
Sometimes the epitope in the foreign protein will be similar to an amino acid sequence in one of our own proteins.
When this happens, the antibody that is generated to bind to and destroy the foreign protein also becomes an autoantibody that can bind to and attack our own bodies.
One well-known example of this is an autoantibody that causes rheumatoid arthritis.
In that case, people get an infection of the gram-negative bacteria P. mirabilis, which is the cause of many urinary tract infections.
One of the epitopes in P. mirabilis, Ile-Arg-Arg-Glu-Thr, is very similar to the amino acid sequence Leu-Arg-Arg-Glu-Ile found in the collagen XI protein of our cartilage.
Once the body detects the P. mirabilis infection and Ile-Arg-Arg-Glu-Thr epitope, antibodies are produced to bind to the bacterial protein and destroy it.
But those same antibodies also bind to the Leu-Arg-Arg-Glu-Ile epitope in the collagen XI protein in cartilage - acting as an autoantibody. This sets off an immune response and inflammation in the joints, causing rheumatoid arthritis.
How do Microclots cause Autoantibody Generation?
So, now we understand how antibodies are made and how they can become autoantibodies that attack our own proteins and bodies.
But how can microclots generate autoantibodies?
Remember that microclots have two major hallmarks:
Microclots are made of polymers of fibrinogen that has been folded into an unnatural conformation.
Microclots bind other proteins and molecular structures in the blood, because they are “sticky”.
When fibrinogen is induced to change into the unnatural conformation (by binding the Covid spike protein), amino acid sequences on fibrinogen that are not naturally seen by the immune system are exposed.
This offers epitopes that the body can see as “foreign” and therefore antibodies can be generated. Those antibodies can turn around and attack the body as autoantibodies, because that epitope is naturally occurring in our bodies.
Similar to fibrinogen, other proteins and molecular structures that bind to microclots can also change into unnatural conformations, again unmasking epitopes that the immune system normally does not see, which can lead to additional autoantibody generation.
So this combination of fibrinogen itself adopting unnatural conformations plus other proteins binding to the microclot and also adopting unnatural conformations presents a large variety of novel and different epitopes to the immune system.
And because microclots will likely form to a different degree in different people and have a range of different proteins bound to the microclots in different people, you get a large range and variety of autoantibodies generated in different people.
So one mechanism - microclots causing a variety of novel epitopes to be presented to the immune system - can cause the generation of a variety of different autoantibodies in different people, that will result in different autoimmune responses.
Understanding all of the autoantibodies that are being generated in Long Covid by this mechanism is a herculean task that will require years of dedicated research to truly understand.
So how do we stop this autoantibody production?
To stop autoantibody production in Long Covid, we have to deal with the microclots.
And as we have seen previously, the only treatment that seems to get rid of microclots and treat Long Covid is Triple Anticoagulant Therapy. You can read about that therapy here, here, and here.
But not everyone is able to get their physician to prescribe Triple Anticoagulant Therapy. Which is why I’m developing a natural supplement with ingredients that have the same mechanisms of action as Triple Anticoagulant Therapy.
If you want to hear more about that natural supplement, come join my email list or the Road to Long Covid Recovery Facebook Group.
And if you want to be notified when my natural supplement is ready, go here to get on the list.
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Reference
Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases? Biochemical Journal 2023, 480, 1217–1240. https://doi.org/10.1042/BCJ20230241.
Very clear explanation, thank you for this