The fact macrophages line the intestine from top to bottom in huge numbers, and the fact our gene variants directly affect the ability of macrophages to clear bacteria, leave very little doubt that CD centers around innate immunodeficiencies. If you stimulate those macrophages or stimulate autophagy in those macrophages (vit D might stimulate autophagy through NOD2), in theory they would have less issues dealing with bacteria and you wouldn't have a chronically stimulated immune system since those macrophages will stop releasing cytokine that stimulate the immune system.JMC this is an interesting proposition, especially if you ascribe to theory that CD is a macrophage deficiency issue. Just going by the abstract it seems it's boosting macrophage secretion, which then goes to normalize the body's natural mechanism for bacterial clearing. I'm going to try to get full article to see if I can digest what it says.
Kiny you seem to have a good grasp of this topic. If you have some time would you mind reviewing this article and providing some feedback on it? It appears to answer a lot of questions surrounding macrophage dysfunction, and even suggests "A basic abnormality in macrophage biology could also explain extraintestinal manifestations of CD, such as arthritis, and lesions in the eyes, skin, lungs, and other tissues"The fact macrophages line the intestine from top to bottom in huge numbers, and the fact our gene variants directly affect the ability of macrophages to clear bacteria, leave very little doubt that CD centers around innate immunodeficiencies. If you stimulate those macrophages or stimulate autophagy in those macrophages (vit D might stimulate autophagy through NOD2), in theory they would have less issues dealing with bacteria and you wouldn't have a chronically stimulated immune system since those macrophages will stop releasing cytokine that stimulate the immune system.
If you look at crohn's disease from an immunodeficiency angle, a lot of things suddenly make sense, particularly our innate immune system, or primary immune system, whatever people choose to call it.
Yes, that is my understanding and it is based on a bacteria that is commonly found in the gut, though I cannot find anything on their website specifying which one (though I am lead to believe it is E-coli)From what I understand the Qubiologics vaccine going on trial in Vancouver is about a treatment that stimulates the macrophages so they can work properly.
There is a description of the MAP vaccine here: http://crohnsmapvaccine.com/vaccine/, a more technical description is available in this paper: http://www.ncbi.nlm.nih.gov/pubmed/...cobacterium+avium+subspecies+paratuberculosis.Is the anti-map vaccine working in similar way?
yes, it would just manifest itself most in the intestine, because of the high concentration of macrophages and peyer's patches there, all other manifestations of the disease would be secondary to what happens in the intestine"A basic abnormality in macrophage biology could also explain extraintestinal manifestations of CD, such as arthritis, and lesions in the eyes, skin, lungs, and other tissues"
And for those following the SSI Trial, their vaccine target is in fact a proprietary strain of AIEC (Adherent Invasive E. Coli).I find MAP in crohn's disease interesting to discuss. But the innate immune response is nonspecific compared to the adapative immune response. Specific immune responses are the job of lymphocytes and their cytotoxic ability to kill bacteria, I think we should consider MAP, but be careful not to put all hope on MAP, because an innate immunodeficiency of macrophages would probably result in many bacteria exploiting those deficiences. MAP and like the article mentions AIEC, just happen to be good candidates, because they're perfect candidates to exploit macrophage deficiencies.
is there an antibiotic in the SSI vaccine just like in the MAP vaccine?And for those following the SSI Trial, their vaccine target is in fact a proprietary strain of AIEC (Adherent Invasive E. Coli).
There isn't an antibiotic in the MAP vaccine, but there are antibiotics against MAPis there an antibiotic in the SSI vaccine just like in the MAP vaccine?
My understanding is that the SSI vaccine is based on a killed strain of a proprietary [Adherent Invasive] E. Coli bacteria. Think flu shot. I would think the mechanism by which it works is it trains the adaptive immune system to recognize this (and similar?) bacteria and stage a secondary defense against it where the innate immune system falls short.is there an antibiotic in the SSI vaccine just like in the MAP vaccine?
yes, I have come across that trial. Plaquenil is widely used in psoriasis and RA and often in combinaition with methotrexate, but I think the reason why its not being used in IBD is for the increased risk of diearrhea with this treatment, but im not sure.You could target AIEC with Hydroxychloroquine, intracellular AIEC is extremely vulnerable to changes in pH, there are some crohn's disease trials where they are using cipro together with Hydroxychloroquine. It's used to kill malaria too. Hopefully there is some better treatment soon.