It’s no picnic, parasites are burly! The Th2 adaptive immune response for worms, our only parasite response, is only good with small initial infections. But since the side effects are relatively mild considering all parasites, it’s not a big area of focus.
Fun fact: The same response for parasites causes allergies. You can never be allergic when it’s your first exposure either. But a less hygenic environment as a kid greatly redices the risk of developing allergies.
Yep! Mast cells are activated when IgE antibodies bind to a mast cell receptor. When IgE then binds to the one object it was designed to find, you get mast cell degranulation. This releases histamines along with a few other chemicals. Degranulation is our immune defense against parasites, so you got a head start for parasite defense for sure! But desensitization can be achieved, which makes IgG antibodies bind to the foreign object before IgE has the chance. I’d think this could be a possible treatment for the syndrome.
Do you also have asthma? The same IgE’s also bind to eosinophil’s. Mast cell degranulation in the lungs leads to acute asthma, whereas when eosinophil’s join the party it causes airway remodeling, aka chronic asthma.
I don’t have asthma. I don’t even think I have any IgE involvement. My total IgE tests at low/normal levels, I don’t seem to have eosinophil involvement that I am aware of. I haven’t even had anaphylaxis before. Though my mast cells constantly degranulate in response to histamine liberators like pepper, chilli, tomato, mustard or triggers like vibrations (shower water on my skin or electric toothbrush), or like laundry scents or perfumes or quick temperature fluctuations or stress or lack of sleep. Gives me maad fatigue, lots of histamine release, blood thinning, etc. Have to avoid triggers and take a bunch of things I found that stabilise mast cells and then I feel good. I have mutations in my methylation and metabolism genes which drains my (acetyl)choline too so probably related somehow.
While there’s no free floating IgE in your system, to degranulate mast cells need IgE bound to their surface. Thats the activation aspect. Since you need mast cells, it’s not exactly something you can turn off. Glad you know the triggers at least, gives you the opportunity to make moves accordingly!
Here’s a great image of degranulation:
You need two IgE’s to cross-link the same antigen as well, like what is shown above.
They always need IgE to activate? How does this work for triggers that have no antigen, e.g. vibrations? Is there any way to identify what the mast cell bound IgE are reacting/binding to?
I understand that there are cases where spinal decompression surgery has cured mast cell activation syndrome. It seems to be related to spinal compression in some cases including mine. Any idea how that could possibly be tying in?
Well, in digging into some research papers, I found “mast cell activation can be caused by both IgE-mediated and non–IgE-mediated triggers”.
This is because there can be a mast cell mutation (KIT) which then doesn’t require IgE for activation. You have MMAS and not Mastocytosis, right? The mutation seems to be associated with Mastocytosis based on my understanding from the paper.
Since mast cells aren’t privileged, they’re restricted from entering sites like the brain and spinal cord. So, if they’re in the spinal cord, you almost certainly have bigger problems than mast cell activation I’d think, as the barrier isn’t doing it’s job.
The BIGGEST issue with our understanding of the immune system today is that ALL testing is done on mice. The human body on a chip technology along with the digitization of the immune system together will be a monumental step. Thankfully, it’s literally something we’ll have in the near future. Once that’s available, we’ll have human specific data plus an onslaught of constant information, which we need to help folks with all of the immune system disorders. I’m an autoimmune patient and losing my friends and family to this uncertainty has led me into the field to try and help improve our understanding. There’s legit more we don’t know than we do know about the human immune system right now.
Facinating, I think non-IgE lines up more with my experience. I believe I have MCAS but doctors don’t really do much testing. I have my full genome sequenced at 100x coverage so I’ll check for the mutation mentioned today! Plus any others if you have suggestions
Good on you for being so knowledgeable about the disorder. But 100% ask your doc, being real with my doc has taken our appointments to the next level. The genome is only half of the IgE allergy response, other half is the environment you were raised in as you can build tolerance of it. A high genetic aspect can be countered by a “low hygienic” environment according to research.
It’s no picnic, parasites are burly! The Th2 adaptive immune response for worms, our only parasite response, is only good with small initial infections. But since the side effects are relatively mild considering all parasites, it’s not a big area of focus.
Fun fact: The same response for parasites causes allergies. You can never be allergic when it’s your first exposure either. But a less hygenic environment as a kid greatly redices the risk of developing allergies.
If I have mast cell activation syndrome, am I less likely to get parasites then?
Yep! Mast cells are activated when IgE antibodies bind to a mast cell receptor. When IgE then binds to the one object it was designed to find, you get mast cell degranulation. This releases histamines along with a few other chemicals. Degranulation is our immune defense against parasites, so you got a head start for parasite defense for sure! But desensitization can be achieved, which makes IgG antibodies bind to the foreign object before IgE has the chance. I’d think this could be a possible treatment for the syndrome.
Do you also have asthma? The same IgE’s also bind to eosinophil’s. Mast cell degranulation in the lungs leads to acute asthma, whereas when eosinophil’s join the party it causes airway remodeling, aka chronic asthma.
I don’t have asthma. I don’t even think I have any IgE involvement. My total IgE tests at low/normal levels, I don’t seem to have eosinophil involvement that I am aware of. I haven’t even had anaphylaxis before. Though my mast cells constantly degranulate in response to histamine liberators like pepper, chilli, tomato, mustard or triggers like vibrations (shower water on my skin or electric toothbrush), or like laundry scents or perfumes or quick temperature fluctuations or stress or lack of sleep. Gives me maad fatigue, lots of histamine release, blood thinning, etc. Have to avoid triggers and take a bunch of things I found that stabilise mast cells and then I feel good. I have mutations in my methylation and metabolism genes which drains my (acetyl)choline too so probably related somehow.
While there’s no free floating IgE in your system, to degranulate mast cells need IgE bound to their surface. Thats the activation aspect. Since you need mast cells, it’s not exactly something you can turn off. Glad you know the triggers at least, gives you the opportunity to make moves accordingly!
Here’s a great image of degranulation:
You need two IgE’s to cross-link the same antigen as well, like what is shown above.
They always need IgE to activate? How does this work for triggers that have no antigen, e.g. vibrations? Is there any way to identify what the mast cell bound IgE are reacting/binding to?
I understand that there are cases where spinal decompression surgery has cured mast cell activation syndrome. It seems to be related to spinal compression in some cases including mine. Any idea how that could possibly be tying in?
Well, in digging into some research papers, I found “mast cell activation can be caused by both IgE-mediated and non–IgE-mediated triggers”.
This is because there can be a mast cell mutation (KIT) which then doesn’t require IgE for activation. You have MMAS and not Mastocytosis, right? The mutation seems to be associated with Mastocytosis based on my understanding from the paper.
Since mast cells aren’t privileged, they’re restricted from entering sites like the brain and spinal cord. So, if they’re in the spinal cord, you almost certainly have bigger problems than mast cell activation I’d think, as the barrier isn’t doing it’s job.
In case you’re interested, here’s the paper on mast cell disorders: https://www.jacionline.org/article/S0091-6749(17)31025-4/fulltext
Here’s one on the brain and spinal cord: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481533/
The BIGGEST issue with our understanding of the immune system today is that ALL testing is done on mice. The human body on a chip technology along with the digitization of the immune system together will be a monumental step. Thankfully, it’s literally something we’ll have in the near future. Once that’s available, we’ll have human specific data plus an onslaught of constant information, which we need to help folks with all of the immune system disorders. I’m an autoimmune patient and losing my friends and family to this uncertainty has led me into the field to try and help improve our understanding. There’s legit more we don’t know than we do know about the human immune system right now.
Lots of SNPs in my KIT but no p.D816V
Facinating, I think non-IgE lines up more with my experience. I believe I have MCAS but doctors don’t really do much testing. I have my full genome sequenced at 100x coverage so I’ll check for the mutation mentioned today! Plus any others if you have suggestions
Good on you for being so knowledgeable about the disorder. But 100% ask your doc, being real with my doc has taken our appointments to the next level. The genome is only half of the IgE allergy response, other half is the environment you were raised in as you can build tolerance of it. A high genetic aspect can be countered by a “low hygienic” environment according to research.