1. RB Birge, the lead author, has NO affiliation with PPHM.
2. Other senior contributors to the paper come from Germany, Brazil, and England. Needless to say, they don't work at UTSW.
3. The paper uses the word "astonishing" to describe the number of major infectious disease pathogens that utilize phosphatidylserine and apoptotic mimicry to evade host immune responses.
4. It is well-known that PS is profoundly dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity.
5. Externalization of PS causes loss of curvature of the cell membrane, which critically affects its ability to communicate with extremely important immune proteins.
From the paper directly:
6. The paper emphasizes "net charges" and the importance of multiple proteins having the "ability to dock" onto the membrane. This is only possible if PS stays internalized. If PS flips externally, everything changes.
(I've been interested in this phenomenon for years. My prior reading from years ago, particularly of Hans Nieper, MD, an oncologist from Hanover, Germany, focused on this area. Nieper knew back in the 1970s that electrostatic changes in the cell membrane placed it outside the grasp of the immune system. He did not know it was phosphatidylserine extroversion that was doing it back then, but his instincts were dead on.)
7. Wolchok's "apoptotic threshold" is explained in the paper:
8. Dysregulation of the apoptotic process results in cells that are supposed to die, but don't. A chronic, inflammatory crippled cell sets the stage for auto-immune disease, whereby the immune system constantly attacks the cell, trying to induce its apoptosis, but instead provokes chronic inflammation.
9. Infectious disease pathogens and neoplasms hijack the normal, homeostatic process of non-inflammatory cell destruction (normal apoptosis) and clean-up for their own survival advantage. These pathogens include the worst of the worst: HIV, HEP B, Ebola, Tuberculosis, Malaria, Syphilis, Meningitis.
10. Phosphatidylserine is recognized WORLD-WIDE as a central player in the lifecycle of every cell in the human body. That by itself should make you think twice before selling your shares.
From the paper directly:
Comments:
The clinical applicability of PS blockade is just stupidly huge. All solid cancers, and most infectious disease pathogens utilize PS to "trick" the immune system into not bothering them.
Any agent that can reverse that hijacking and thereby render the offending pathogen once again suspectible to immune system attack would be, as the paper states, "attractive."
That agent is Bavituximab, the central ingredient in the gazillion dollar I/O stew. (Remember, a "central ingredient" has to present on EVERY SINGLE CELL.)