I guess it makes sense that the 1,25 could be high due to the activated macrophages, but what is activating them? I know too many questions.
That being said -- hopefully I can ask just two more questions: Did you/do you have any classical sarc-like symptoms? And has anyone been able to explain why you're in the 10% that has elevated blood calcium rather than low calcium?
My opinion is that it's an underlying bacterial/viral/whatever cause that is causing the macrophages to be activated. Body is trying continuously to get rid of it, but since it's not successful it just keeps trying.
As Sushi mentioned, LPS can activate macrophages. LPS is an endotoxin. From Wikipedia's endotoxin entry:
The term
endotoxin was coined by
Nats Umangay, who distinguished between
exotoxin, which he classified as a toxin that is released by bacteria into the environment, and endotoxin, which he considered to be a toxin kept "within" the bacterial cell and to be released only after destruction of the bacterial cell wall. Today, the term 'endotoxin' is used synonymously with the term
lipopolysaccharide[citation needed], which is a major constituent of the outer cell membrane of
Gram-negative bacteria. Larger amounts of endotoxins can be mobilized if Gram-negative bacteria are killed or destroyed by detergents. The term "endotoxin" came from the discovery that portions of Gram-negative bacteria themselves can cause
toxicity, hence the name endotoxin. Studies of endotoxin over the next 50 years revealed that the effects of "endotoxin" are, in fact, due to lipopolysaccharide.
The key effects of endotoxins on vertebrates are mediated by their interaction with specific receptors on immune cells such as
monocytes,
macrophages,
dendritic cells, and others. Upon challenge with endotoxin, these cells form a broad spectrum of immune mediators such as
cytokines,
nitric oxide, and
eicosanoids.
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With respect to my own personal situation, nobody has even given me a diagnosis, much less an explanation! I don't think I have any sarc symptoms (I don't even really believe I have sarc - it's just the closest "label" that corresponds to some of my lab data, namely the high 1,25D and hypercalcemia). When I first started researching it last year, I found that others besides Marshall (e.g. Moller and Drake at Vanderbilt) think that sarc may have a bacterial cause, that's why I've decided not to get too caught up in a specific diagnosis, and instead focus on treatment - acting as if it's a bacterial/viral infection. Whether it's technically sarc or not is of no real concern to me since I will pursue the same treatment regardless.
Something else I find interesting in my medical puzzle is that my (now deceased) mother had TB multiple times in her life (or perhaps it was one chronic infection that went on for many many years)...I have to believe that's significant (from an exposure and/or genetic point of view).