@
alex3619 have you read this:
Although ferritin is widely recognized as being secreted by hepatocytes and
macrophages, its production by the mast cell [195] is far less appreciated. Hyperferritinemia
is quite common in mast cell disease [62], yet often it is misinterpreted as hemochromatosis
(even in the absence of an identifiable HFE mutation) or, in the patient who has received red
cell transfusions for any reasons, hemosiderosis. [196] It can be tempting to attribute the
entirety of the observed hyperferritinemia in an MCAS patient to transfusional hemosiderosis
if the patient has any transfusion history, but two clues will suggest that a not insignificant
portion of the elevation in ferritin is of inflammatory origin. First, the serum ferritin level
often is considerably higher than would be expected purely from the degree of hemosiderosis
attendant to the extent of the transfusion history. Second, while the hyperferritinemia of
transfusional hemosiderosis marches in relative lockstep with the transfusion history, the
hyperferritinemia of inflammation (MCAS-driven or otherwise) is highly variable from one
determination to the next.
Mast cell disease has been clearly associated with obesity and with diabetes mellitus
(both types) [197, 198]; of note, both obesity and diabetes mellitus (both types) are now
clearly recognized as chronic systemic inflammatory conditions. Mast cells have been
identified as effector cells in metabolic syndrome, too. [199] Given the intimate involvement
of PGD2 and its metabolites in at least one key adipose management pathway [200], it is not
surprising that there is a surfeit of lipid abnormalities in MCAS, too. [63] Elevations in total
cholesterol and low-density lipoproteins, and decreases in high-density lipoproteins and verylow-
density lipoproteins, are not uncommon. [197] Hypertriglyceridemia, too, is common and
often is the starkest lipid abnormality.
This is a differential diagnosis I will have to have investigated of course. It is interesting they discuss iron levels and transfusion, and that in MCAS the iron levels do not reflect the degree of transfusion. My docs could make the same mistake with respect to haemochromatosis. My iron is going up too fast for haemochromatosis.
Essentially there are two issues. Iron absorption, and iron release. My water supply needs to be tested for iron. I need to be tested for mast cell activation. Yet mast cell activation does not create iron. It causes it to be released, primarily I suspect from the liver. Now the fact I am a haemochromatosis carrier might mean I have far more iron in my liver, so when released it creates a massive iron spike. This however should resolve with time, as the iron is finite, particularly if MCAS (or liver infection) is indentified and controlled.
If MCAS or an infection is the cause than treatment for haemochromatosis should work and lower my iron. If I have a source of ongoing iron poisoning though, treatment will only slow the problem down a little.
Questions, questions, always questions. The right question is important if you want the right answer.
I have elsewhere proposed that ME is also a PGD2 disorder, but possibly not from mast cells. Contrary to what immune focused research claims, brain focus research claims the brain is the main source of PGD2. Everybody makes it, every day, and its linked to our sleep cycles. PGD2 is what actually switches the brain off in sleep, all the other stuff including melatonin is about regulating PGD2.
So if we make too much in the brain, we are sleepy all the time, and parts of the brain might actually be asleep ... the whole brain does not have to sleep at one time. This would create holes in our brain function, and localized hypometabolism ... which is what we see. Of course this interpretation does not completely rule out mast cell involvement.
ME certainly involves biochemistry that would drive PGD2 synthesis, because of bad regulation of eicosanoids due to inflammation, decreased glutathione, nitric oxide and peroxynitrite. Of course having such biochemistry does not tell you
where this happens, or even
if it happens, only that it can.
Anyway, thanks for the article @
leela. I will definitely be raising this issue, but I wonder if I am going to get hit with a side-diagnosis of hypochrondria, doh.