Defective acute inflammation in Crohn’s disease: a clinical investigation

[kiny]

Defective acute inflammation in Crohn’s disease: a clinical investigation

Linking it because it's hard to wrap your head around crohn being an immunodeficiency, this is the earliest study I have read and started to realise there are immunodeficiencies in crohn, the whole disease is related to immunodeficiencies. Especially autophagy and the primary inflammatory response is completely compromised in crohn's disease patients, if relevant the hygiene theory would further compromise the acquired immune response leading to more immunodeficiencies.

Patients with crohn's disease, not on immunosupressive drugs, with an optimal nutritional status.

Against controls, with similar age, nutritional status, without crohn's disease.


They did a biopsy on them, and they checked the inflammatory response and healing. People with crohn's disease had lowered neutrophil response and took longer to heal.

They wondered if this immunodeficiency was localised in the gut or everywhere. So they infected the arm of people (with a small slit) with prepared bacteria (E coli type) and checked what happened.

People with crohn's disease had again, a weaker innate immune response, took longer to clear the bacteria and longer to heal.



Those recent studies that showed death rates for crohn's disease have not gone down in decades, partly because of the big number of infections people with crohn's disease are getting, because of the immunosupressive drugs, the clinical environment they are in, and their genetic and acquired immunodeficiencies (genes, hygiene theory).

If the top-down approach was used everywhere, deaths for crohn's disease would have likely been higher in the last decades than before, long-term use of immunosupressive drugs carries huge risks when given to an immunodeficient person who is constantly in a hazardous medical environment.

Some of the drugs that were approved for crohn's disease were approved on the condition that they would lower deaths related to crohn's disease. Evidence has shown this is not the case, since deaths are not going down.

Some GI should really start thinking what they are doing with a disease that is spreading worldwide, how ignoring evidence is hurting people with crohn's disease, and how current treatment with immunosupressive drugs is not a solution for crohn's disease and never will be.

You can not walk the road of veduzolimab (and all the trials before where you killed people) and interleukin blockers and keep endangering the lives of people with crohn's disease. The constant revenue stream of immunosupressive drugs not only makes GI liable when they put profits in front of patient care, they endanger the lives of people.

The evidence is there, if you take profits over care, someone will one day show how you ignored evidence in favor of profits and they'll tell you, you were liable.

I 100% agree with the German paper that veto'd veduzolimab and interleukin blockers. You better have the best lawyer in town when a person on veduzolimab gets a brain infection, since many many people have warned you.

 

[rollinstone]

Thanks for the post kiny,

 

[Jam300]

Thanks Kiny, very interesing read.

 

[mf15]

Kiny: You may remember these studies where they stimulate the immune system.
Old Mike
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2621411/

 

[David]

Kiny, how would you suggest it be treated?

 

[kiny]

Like you would treat Chronic granulomatous disease, test for bacterial susceptibility, immunoglobulin issues (is done sometimes), and ultimately treat the disease like we treat other PID (primary immunodeficiency disease), keeping in mind that supression of the immune system in an immune compromised person is high risk.

People with crohn's disease should not be an experimental platform for drugs that later on get used for RA or some other autoimmune diseases.

Crohn's disease should be treated keeping in mind that it's an immunodeficiency of macrophages and autophagy.

Current immunosupressive drugs offer a constant revenue stream for pharmaceutical companies and leave patients vulnerable to infections, that the rates of deaths for crohn's disease have not gone down in decades should be a wake-up call to people that the current treatment is anything but reasonable.

Forgot who said it, but "most crohn's disease patients do not want to be chained to lifelong drugs of immunosupressive medication", it's unsafe and leaves people with much too high risk of infections.

 

[David]

I'm not familiar with the treatment protocol for other PID. What is it?

 

[kiny]

Depends on the disease, some diseases require immuno modulation through IV immunoglobulin, others require antivirals, others require anti-microbial agents.

Crohn's disease has issues with autophagy and cytokine production, which implies intracellular bacteria to be specific, mycobacteria, listeria, mycoplasma and others. Susceptibility for infectious agents should be done in people and any immune deficiencies should be corrected instead of supressed.

Nutritional therapy to stimulate autophagy, tight control on vitamin D to correct NOD2 autophagy signaling etc.

 

[kiny]

The issue is also that currently antibiotics are given in crohn's disease without susceptibility testing, so you get lots of people saying that their antibiotic worked for 2 weeks and then stopped working, if correct susceptibility testing was done and this disease was recognised as a PID, like it should be, there would be no antibiotics ABUSE, like there is now. GI are screwing people over in treatment because no one is correctly tested before they use antibiotics during fistula and bleedings.

When those people CAN get benefit from anti-microbial agents or get infections, which is common in crohn's disease, they now have one less way to get proper treatment since they allowed for resistance to happen.

Crohn's disease should be treated on an individual basis just like other PID are done, currently the only marker most GI use is calprotectin or crp and they call it a day and just use a dartboard to treat people.

If x doesn't work they try y and if y doesn't work they try z, without actualy knowing what is going on with the patient at all and without taking current research into account that points to a primary immunodeficiency.

 

[kiny]

I also personally think that in studies they should try to keep UC seperated from crohn's disease.

UC is a disease that has an autoimmune response directed at epithelial cells, the colon. UC is mucosal, it's topical if you wish, it does not have the autophagy issues, much lower to insignfificant NOD2 issues, it's just a different disease.

Crohn's disease is a transmural disease, it's deep in the intestine, it has no autoimmune response, it's a lot like Chronic granulomatous disease in a way. It does not have the full blown inflammation over the whole organ like UC has, it has skip lesions like TB has, a sign of bacterial involvement.

The use of "IBD" does not help UC nor does it help Crohn's disease, it implies that these disease are similar and treatment should be similar, when in actuality, treatment for a disease that has an autoimmune component against colon cells is not the same treatment that should be used to treat a PID diease like crohn's disease, in fact some studies have pointed out that using immunosupressives when macrophage function is so compromised in people witrh crohn's disease is counterproductive.

Clinically it's not hard to differentiabe UC from crohn's disease, but it's pretty hard to differentiate it from intestinal TB or chronic granulomatous disease.

Why is UC under an umbrella together with crohn's disease, it makes no sense at all.

The use of the word "IBD" hurts progress for both UC and Crohn's disease.

 

[kiny]

While I'm writing.

I think it is extremely extremely sad that patients are left out of this discussion.

If there is no evidence of autoimmune and no evidence of any self-targeted attack against epithelial cells, no real evidence of an attack against commensals, why is this currently an acceptable way to explain crohn's disease?

The evidence of immunodeficiencies ARE THERE, they are RIGHT THERE in black and white, I made a timetable, the immnodeficiencies have been there since 1976 when deficiencies in neutrophil response were shown. (even a few years earlier there were some studies that suggested this)

1976 Neutrophil dysfunction in Crohn's disease.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2876%2991024-2/abstract

They can be clinically reproduced in every study, and genes 100% support this evidence.

Don't leave patients on the crossroads while some people make up their mind. The evidence is there. It's time for change.

 

[wild_one353]

i will have to take time to carefully evaluate the entire study, but one thought comes to mind, how do we know that this slower/weaker overall immune reaction isnt just a effect of the disease itself? im not sure where it is justified to say this could be the cause of the disease, and ignore so much other information we have about the state of the body and epidemiological information when proposing a theory of a cause.

but they were simply evaluating a theory, to see if they could find information to "fit" the theory of immune deficiency as a sole cause. rather then acknowledge the bulk and totality of the existing science, which may contradict the theory.

to say crohn's disease is "like" chronic granulomatous disease, im not sure we can say it is "like" it, but as far as i recall a granuloma is generally formed to block the invasion of something into the body, to form another barrier, like a replacement skin. its been proven that one of the main causes of CGD is a genetic mutation seriously affecting the function of the nadph oxidase enzyme that enables the killing of bacteria. this is a major defect, and in crohns, no similar equivalant in genes has been found.

I would think that in CGD since the body has a hard time killing the invador, blocking its entrance would be a secondary strategy, hence the granuloma formation. so then if we find a granuloma in crohn's disease, does that mean we cannot kill the bacteria? or that the bacteria is so large in number, and that is the only reason it cannot be killed, and therefore that is the only reason a blocking strategy is utilized, not because of a a serious defect in ability to engulf and kill. to find a granuloma in crohn's does not mean it is going to be just like CGD, granuloma may only be blocking bacteria and other foreigns objects independantly of any reduced ability to kill or engulf/destroy.

everything i just said is simply my general and slightly educated opinion.

 

[kiny]

i will have to take time to carefully evaluate the entire study, but one thought comes to mind, how do we know that this slower/weaker overall immune reaction isnt just a effect of the disease itself? im not sure where it is justified to say this could be the cause of the disease, and ignore so much other information we have about the state of the body and epidemiological information when proposing a theory of a cause.

but they were simply evaluating a theory, to see if they could find information to "fit" the theory of immune deficiency as a sole cause. rather then acknowledge the bulk and totality of the existing science, which may contradict the theory.

It's supported by genetic studies, the tests were done on people not on any medication that modulates the inflammatory response, it's not localised in the intestine.

Let's say an agent was modifying the immune response, we treat AIDS as an immunodeficiency.

 

[kiny]

rather then acknowledge the bulk and totality of the existing science, which may contradict the theory.

which bulk of science is that, still need to read the first study that shows an autoantigen in crohn's disease

Autoimmune requires an autoantigen, a self-directed immune response would not be patchy, it would not have this chronic pattern crohn's disease has.

Directed immune response at commensals, kind of doubt it, would be the first disease in history where this happens, crohn's disease is transmural, I don't believe in it.

Immnodeficiency, we know this, can measure it, and it's supported by genetic studies.


The bulk of science supports immunodeficiency.

 

[kiny]

Not sure what you're trying to say about CGD, clinical symptoms can be very similar to crohn's disease, and it features a primary immunodeficiency like CD does. It fits the bill of crohn's disease much better than UC does, which is nothing like CD.

 

[wild_one353]

which bulk of science is that, still need to read the first study that shows an autoantigen in crohn's disease

Autoimmune requires an autoantigen, a self-directed immune response would not be patchy, it would not have this chronic pattern crohn's disease has.

Directed immune response at commensals, kind of doubt it, would be the first disease in history where this happens, crohn's disease is transmural, I don't believe in it.

Immnodeficiency, we know this, can measure it, and it's supported by genetic studies.


The bulk of science supports immunodeficiency.

oh im not doubting that it could be right, or you could be right, you absolutly could be right, you are likley more well read and educated then me. but how will immunodeificiency theory be proven conclusively? im not sure.

i will have to read about what the fact of crohns being transmural, exactly means? i mean beyond the general definition of, inflammation throughout the intestinal wall. exactly what does that require us to conclude about the disease? i really dont know, i am open to you elaborating on this though, maybe you could help me understand the significance and how to interpret what transmural inflammation would indicate and what that tells us about crohn's disease.

 

[kiny]

I would think that in CGD since the body has a hard time killing the invador, blocking its entrance would be a secondary strategy, hence the granuloma formation. so then if we find a granuloma in crohn's disease, does that mean we cannot kill the bacteria? or that the bacteria is so large in number, and that is the only reason it cannot be killed, and therefore that is the only reason a blocking strategy is utilized, not because of a a serious defect in ability to engulf and kill. to find a granuloma in crohn's does not mean it is going to be just like CGD, granuloma may only be blocking bacteria and other foreigns objects independantly of any reduced ability to kill or engulf/destroy.

everything i just said is simply my general and slightly educated opinion.

If we can't properly complete the autophagy step at the macrophage level the infection would persist, I don't think you would need large numbers of bacteria to create a crohnic infection, you'd need very few to keep an inflammatory reaction going.

 

[kiny]

i will have to read about what the fact of crohns being transmural, exactly means? i mean beyond the general definition of, inflammation throughout the intestinal wall. exactly what does that require us to conclude about the disease?

If the disease is transmural and the early events of crohn's disease start in submucosa up to the mesentery it means the theory of an uncontrolled reaction against commensals loses credibility.

I question if our indigenous flora has anyhting to do with crohn's disease at all, I doubt it. There hasn't been a single disease in history where our immune system attacks our own flora.

 

[kiny]

how will immunodeificiency theory be proven conclusively? im not sure.

 

[wild_one353]

If the disease is transmural and the early events of crohn's disease start in submucosa up to the mesentery it means the theory of an uncontrolled reaction against commensals loses credibility.

ok cool. the fact that the disease is transmural , you interpret this as possibly suggestive that this is an early event and this is where the disease started. where is the evidence showing this to be an early event, transmural inflammation is the fact, while when it occurs and in what order is the theory, and not a proven fact.
what evidence exists within the literature that proves or strongly suggests that inflammation starts in the submucosa, and precedes and involvement of the mucosa and gut flora? if that premise is even remotely establised, you will have provided a good case to me, i doubt the evidence exists, i do not doubt its possibility of being true.

BTW, im not endorsing nor defending nor trying to prove a theory of immune reaction to commmensals as the one-and-only or one-of-the-many-possible cause's of crohn's disease.

I question if our indigenous flora has anyhting to do with crohn's disease at all, I doubt it. There hasn't been a single disease in history where our immune system attacks our own flora.

Kiny i like you alot, and this is just my casual observation, but you seem a little biased in a negative way as a researcher. to doubt a theory on the grounds as simple as, "it has never been true before, therefore it cannot be true now", is not justified and sort of dogmatic. i have seen studies saying that there seems to be a specific response towards commensals i think towards some strains of bacteroides species which is often abnormally raised in Crohn's, but in my opinion that is not an explanation of the cause of crohn's disease, that is just one of many facts.

 

[wild_one353]

I agree the presence of an immunodeficient state in crohns patients is proven to some degree, but evidence that immunodeficient state as being the cause of crohns disease, has that been clearly demonstrated? im honestly asking you, and not being rhetorical. how exactly would one prove that? again, honestly asking not being rhetorical.

 

[kiny]

ok cool. the fact that the disease is transmural , you interpret this as possibly suggestive that this is an early event and this is where the disease started. where is the evidence showing this to be an early event, transmural inflammation is the fact, while when it occurs and in what order is the theory, and not a proven fact.

Well, go look at histology pictures and tell me what you think it looks like. Early crohn's disease looks like apthae and protruding lymphoid follicles, doesn't look like mucosal involvement is first to me at least.

That the disease is transmural we know.

What's it look like to you?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396064/pdf/ijcep0005-0411.pdf

 

[kiny]

i have seen studies saying that there seems to be a specific response towards commensals i think towards some strains of bacteroides species

Ok I'll ask you a question then, Which study was that.

 

[wild_one353]

Ok I'll ask you a question then, Which study was that.

here is some info i believe along the lines that i had mentioned previously.

http://www.ncbi.nlm.nih.gov/pubmed/21484962

http://gut.bmj.com/content/44/6/812.full.pdf

 

[wild_one353]

Well, go look at histology pictures and tell me what you think it looks like. Early crohn's disease looks like apthae and protruding lymphoid follicles, doesn't look like mucosal involvement is first to me at least.

That the disease is transmural we know.

What's it look like to you?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396064/pdf/ijcep0005-0411.pdf

its break time for me now but i will read through and try to understand this, and i appreciate you showing this to me.

 

[Malgrave]

Thanks Kiny! Very interesting discussion indeed!
All I can add at this moment is that my 5 years old son has now been on IVIG for 2 months and he has never felt better during his 3 years of this horrible disease. Befofe starting the IVIG he was bleeding daily for more than a year. Remicade made him very very sick. After 4 weeks from the start of the IVIG the bleeding stopped, which is for us a real miracle!!!

 

[kiny]

here is some info i believe along the lines that i had mentioned previously.

http://www.ncbi.nlm.nih.gov/pubmed/21484962

http://gut.bmj.com/content/44/6/812.full.pdf

Bacteroides and Bifidobacterium are colon commensals, if the immune response was directed at them our whole colon would be inflamed, and for most people it's just the terminal ileum, it wouldn't be patchy either.

 

[rollinstone]

Thanks Kiny! Very interesting discussion indeed!
All I can add at this moment is that my 5 years old son has now been on IVIG for 2 months and he has never felt better during his 3 years of this horrible disease. Befofe starting the IVIG he was bleeding daily for more than a year. Remicade made him very very sick. After 4 weeks from the start of the IVIG the bleeding stopped, which is for us a real miracle!!!

Forgive my ignorance, what is IVIG?

 

[Farmwife]

Joshuaaa,
I was wondering the same thing.
Malgrave what is IVIG?

 

[rollinstone]

Joshuaaa,
I was wondering the same thing.
Malgrave what is IVIG?

I looked it up, it's intravenous immunoglobulin

 

[wild_one353]

Well, go look at histology pictures and tell me what you think it looks like. Early crohn's disease looks like apthae and protruding lymphoid follicles, doesn't look like mucosal involvement is first to me at least.

That the disease is transmural we know.

What's it look like to you?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3396064/pdf/ijcep0005-0411.pdf

kiny, so i tried my best to understand what this study was about, as far as i could tell, their may be some misunderstanding on how they use the term pathogenesis that may be confusing. They dont seem to mean that they are attempting to identify a sole cause or have even achieved that in this study. when they use the term pathogenesis, they are just talking about getting more information regarding the order of events, not the absolute first event in crohn's disease.

This study seemed to simply find out more about the role of lymphoid follicles in the development of a crohns lesion, and established a sign/marker, the Red Ring Sign, as an early marker for the development of a crohn's lesion for endoscopic evaluation/determination of crohn's disease, so it seems this study may eventually help a doctor diagnose crohns disease, with more precision, that's all. its not attempting to claim that the immune system is solely responsible for the endoscopic mucosal lesions.

Also, the lymphoid follicles are collections of lymphocytes of varying size, the largest of which are found in the tonsils, peyers patches, and appendix, and most are located directly under the epithelial lining, which is the first layer of the intestinal mucosa, which is not as deep as the submucosa, which this study does not cover.

here is a quote from the study:

The follicle-associated epithelium (FAE) provides a route of entry for antigens and microorganisms. Specialized epithelial M cells of the FAEdeliver samples of antigens from the lumen directly to intraepithelial lymphoid cells and to organized lymphoid tissue, also playing a key role in the invasion of certain bacteria and viruses [9].
LFs (lymphoid follicles) have always been thought to be the main portal of entry for potential pathogens, and it has been suggested that aphthous ulceration in Crohn disease (CD) originates in FAE over the LFs [4, 10, 11]. The pathogenesis of the ulcerating lesions in IBD was the subject of several studies, trying to provide a better insight into the pathogenesis of the disease [6, 12, 13].

Now this is actually just confirming existing science that we seem to already know about the lymphoid follicles, only adding specifically new knowledge relating to crohn's disease, such as the red ring sign as an actual marker of a crohns ulcer, and confirming that ulcers start directly over/above a lymphoid follicle.

here is a quote from a textbook, Essential Histology By David H. Cormack 2001. Page 163.

LYMPHOID FOLLICLES

The loose connective tissue associated with the epithelial linings of the digestive, respiratory and urinary tracts, commonly contains more or less spherical groups of small lymphocytes known as lymphoid follicles(nodules). these accumulations of lymphocytes are not confined by surrounding connective tissues capsules. most lymphoid follicles are solitary small and discrete with a diameter approaching 1mm or so. at certain sites, lymphoid follicles are multiple, large and confluent. such sites include the tonsils, peyers patches, and the appendix.

GUT ASSOCIATED LYMPHOID TISSUE

A marginally higher level of complexity is present in permanant aggregates of lymphoid Follicles that are multiple confluent and large. foreign antigens that penetrate a mucosal epithelium diffuse through the lamina propria. furthermore the epithelial coverings of the palatine tonsils, peyers patches(ileum), and also the epithelial lining of the appendix are provided with special flat epithelial cells known as m(membrane like) cells or FAE(follicle associated epithelial) cells. these thinly stretched dome shaped cells ingest tiny amounts of antigens entering the gut lumen and deliver them to antigen presenting cells and lymphocytes of the gut associated lymphoid tissue. Antigen sampling by these flat epithelial cells is an important preliminary stage in the formation of Iga producing plasma cells. the secretory iga secreted onto the free surface of the mucosal epithilia represents a primary mucosal defense mechanism against infection because appropriate antigen specific iga's are able to decrease microbial adhesion to host cells and neutralize bacterial toxins and viruses.

when they state in the study, "lymphoid follicles may play a crucial role for in the pathogenesis of inflammatory bowel disease (IBD), especially in Crohn’s disease (CD) as the site of initial mucosal inflammation", they said very clearly, mucosal inflammation, not submucosal inflammation. also when they say "site" they mean along the inside of the intestine, not within the depth of intestinal wall, even though the samples they took for confocal laser microscopy were showing the depth of the wall, but that seemed to enable a presentation of an association of the epithelial layer with the red ring phenomenon they were studying with the underlying lymphoid follicle, , showing that the red ring was directly above it.


this link/study has not provided enough evidence to support the claim that the immune system defects or inflammation within the submucosa, precedes all events which trigger crohns inflammation or ulceration, or is the sole cause of crohns disease. nor does it support the claim that the are NO events/molecules that originate from the lumen that precede the onset of crohn's, inflammation or mucosal lesions/ulceration.

Therefore, it is still a possibility that either the disease could be solely initiated from an event or molecules originating in the lumen, such as, a pathogen, or dysbiotic state of intestinal flora or a combination of the two. I was hoping you could provide some evidence that would tell me that the sole cause of crohn's disease absolutly cannot originate from the lumen or start in the epithelial/mucosa, such as a pathogen or a state of dysbiosis. this study does not achieve that.

Thanks kiny for showing me this study, it almost seemed like it would have proven your point, but not quite.

 

[ellie]

A couple of personal observations, from a limited "sample group" of 1 (this may be better presented on a different forum thread!)

i) Since the obvious onset of Crohn's Disease 7years ago, I have had almost NO viral infections, despite living in a busy family unit, and working in a hospital setting.. dealing with a wide range of people on a daily basis, usually without any specific protective measures. Comment from my GI was that this was not unusual in CD!

ii) Again since my CD Dx, any antibiotic use is likely to provoke a flare in my Crohn's activity.. fortunately I haven't had much indication to take them!

I am only taking sulfasalazine, VitD, fish oil, probiotics, so my immune system is fairly unaltered.

So, my question relates to the paradox:

Certainly there are genetic and immunological aspects to CD.
If Crohn's implies a defect in immunity, why do I seem to have more resistance to many of the generally circulating infective agents?
And, apart from the obvious aspect of antibiotics killing off the "good" gut flora, is there something else going on that provokes a flare when antibiotics are indicated?

Would welcome any thoughts or relevant scientific links



HD

 

[kiny]

it almost seemed like it would have proven your point, but not quite.

Remember to stop trying to help you next time, I thought GI were stubborn people. The fact someone as stubborn as you has an incredibly hard time to weasel their way out of the theory, now trying to argue semantics, means it's pretty sound don't you think.

No one said dysbiosis is not related to crohn's disease, dysbiosis would allow for intracellular pathogens to enter, the gut flora is part of our immune system and the first defense against intracellular pathogens. What I do not take for granted is that the immune response is directed at commensals, simply because inflammation is transmural and patchy, which does not bode well for the commensal theory, nor has a directed immune response against commensals ever been at the basis of any disease in history. AIEC are no longer commensals, they are no longer part of the indigenous flora, they are purely pathogenic in nature, in fact they exploit the autophagy step.

It's one thing to have someone who questions what people are saying, it's another to have someone constantly trying to find a new angle to prove science wrong without understanding half of it. It's like trying to argue with a child who already made up his mind that everything is wrong.

I do not have all the answers, I did not write the papers, if you think someone is wrong go ask the people who wrote the papers instead of barraging me with questions without looking up anything yourself. It would be nice to give your own theory or reasoning instead of trying to shoot down studies you don't understand.

You're doing this stuff on purpose to annoy me. I do this to help, you don't, you're the first person I can't stand on this forum, I have seen you do it with other people until they get angry at you. Now you can say I am rude etc, well so be it, I was nice to you for a whole thread, and i thought you would stop, but you willl keep going and going until you successfully trolled the other person and they are upset with you, now arguing semantics, I won't grant you that feeling.

 

[kiny]

A couple of personal observations, from a limited "sample group" of 1 (this may be better presented on a different forum thread!)

i) Since the obvious onset of Crohn's Disease 7years ago, I have had almost NO viral infections, despite living in a busy family unit, and working in a hospital setting.. dealing with a wide range of people on a daily basis, usually without any specific protective measures. Comment from my GI was that this was not unusual in CD!

ii) Again since my CD Dx, any antibiotic use is likely to provoke a flare in my Crohn's activity.. fortunately I haven't had much indication to take them!

I am only taking sulfasalazine, VitD, fish oil, probiotics, so my immune system is fairly unaltered.

So, my question relates to the paradox:

Certainly there are genetic and immunological aspects to CD.
If Crohn's implies a defect in immunity, why do I seem to have more resistance to many of the generally circulating infective agents?
And, apart from the obvious aspect of antibiotics killing off the "good" gut flora, is there something else going on that provokes a flare when antibiotics are indicated?

Would welcome any thoughts or relevant scientific links



HD

Don't know, not sure if viral infections are that important in crohn's disease, most predispositions are related to clearance of intracellular bacteria, mycobacteria in particular. I don't think we can decide for ourselves if we have immunodeficiencies related to intracellular bacteria, we're not exposed to them like we used to, TB and Leprae bacteria are extremely uncommon where I live, even though 6 out of 8 loci match those of leprosy in CD. We wouldn't know if we had these immunodeficiencies ourselves.

Many people in the West have NOD2 and ATG16L1 immunodefiencies and do not have crohn's disease, why does someone get crohn's disease and another person does not. Why can someone carry H Pylori and TB and not be sick, it's not something we can just guess by anecdotal evidence. I have no clue if I get more viral infections or not, it's not something I am capable of deciding on my own.

 

[rollinstone]

Hi kiny, I watched some videos on dr borody discussing MAP as a causative of Crohn's and he explained its already been a proven cause by Koch's postulates. My question for you is, have you tried anti MAP theory (if you don't mind me asking), he said most GI's and physicians dont know of Koch's postulates proving MAP as a causative for Crohn's in up to 50% of people with Crohn's

 

[kiny]

Hi kiny, I watched some videos on dr borody discussing MAP as a causative of Crohn's and he explained its already been a proven cause by Koch's postulates. My question for you is, have you tried anti MAP theory (if you don't mind me asking), he said most GI's and physicians dont know of Koch's postulates proving MAP as a causative for Crohn's in up to 50% of people with Crohn's

Hey. We (me and someone in the lab where they can do PCR testing) both got tested for MAP in blood and both turned up negative. That doesn't mean we don't have MAP, it just means it's negative or false negative, I don't think it would show up in blood easily, it might be more easily detected in abscess or fistula or deeper towards the mesentery.

I don't remember what borody uses, I think he uses clarithromycin, clofazimine, and rifabutin. I think the issue with that is that if MAP is the cause, those anbitiocs are going to be a lifelong treatment, you would need antibiotics that can target non-dividing cells or some vaccine.

The controversy requires an effort and willingness on the part of governments and GI to acknowledge the fact this is possibly a zoonotic agent. Detection methods need to improve and if there is a definitive causal link, there needs to be determined which strains are susceptible to which anti-microbial agents, you don't want to put people on lifelong antibiotics treatments.

The controversy did not go away, it only got worse after the study Nature published that showed the link to mycobacterial susceptibility in which I think is the biggest pool of people for crohn's disease tested for susceptibility for mycobacteria to date. (14.000 people with crohn's disease)

But to solve this controversy, you need willingness on the part of GI, to acknowledge their own data, which for some ridiculous reason, they refuse to do.

 

[rollinstone]

Well MAP is a cause without a doubt (in atleast a large quantity of people), it's been proven, yea that is the problem though, however in comparison to other medications people use for Crohn's they tend to be life long also, Dr Borody also suggested maybe remicade alongside triple anti map therapy as remicade can kill the cells. There have been rare cases where this combo has left people in remission even after discontinuation of anti map therapy, problem is map can take so long to build up it could only be a matter of time until it resurfaces its ugly head. But I do strongly feel that Crohn's is caused by an infective agent. I think it will be like the whole stomach ulcer ordeal that happened years ago, so many physicians chose to ignore it. Give it a few years, we need more researchers and doctors like professor borody, hopefully the rest of the GI world will wake up. I asked my GP about MAP and he told me we don't have it in Australia :s Im gonna ask my GI this week if I can get tested for it.

 

[kiny]

Yes, not sure. I think it would be multiple agents, immunodeficiency and inability to clear bacteria would lead to constant infections that would tax the lymphatic system, until you get lymph drainage issues, you'd get a form of lymphangitis and you would get continuous inflammation because you're unable to deal with antigen content, and the inflammation would not stop, you'd get the clinical granuloma later on. I just don't think it would be one single bacteria, would probably be different bacteria for different people.

I agree with the way infliximab works, I think it works as a type of selective antibiotic through apoptosis, etanercept which is a TNF-alpha blocker does not work for crohn's disease at all. I think that's why so many drugs for RA do not work for Crohn's disease. Lowering the inflammation would not be infliximab's primary mechanic, it would be a result of it's anti-microbial properties.

Etanercept is the best example, it's a TNF-alpha blocker that doesn't work for crohn's disease even though it's just as potent as infliximab. Infliximab causes apoptosis of activated lymphocytes, etanercept does not. It makes infliximab into an anti-microbial agent in the right people, especially people who would have issues with the autophagy step.

 

[Sue-2009]

So, what is the answer to living with crohns? I'm confused?

 

[Maree.]

Kiny thnak you so much for all the fantastic information you shared here and the time you took to explain it and answer questions.

 

[Crohn2357]

If x doesn't work they try y and if y doesn't work they try z, without actualy knowing what is going on with the patient at all and without taking current research into account that points to a primary immunodeficiency.

http://www.ted.com/talks/susan_solomon_the_promise_of_research_with_stem_cells
http://www.ted.com/talks/nina_tandon_could_tissue_engineering_mean_personalized_medicine

A research:http://www.ccfa.org/research/current-research-studies/ibd-genetics-video.html