Kickas.org Forums Ankylosing Spondylitis General Discussion #1 AS Web Support Group Where is the media? Where are the doctor's?

Dear Gerard, it would not at all be surprising that a pathogenic bacterium such as klebsiella would induce the production of an inflammatory cytokine like TNF alpha, but of course a variety of other pathogenic organisms could also induce the production of proinflammatory cytokines.

The study you cited does not really replicate the complexity of the host-gut microorganism interaction in vivo, because as far as I could tell by looking at the abstract you cited, that study is introducing a microorganism species singly to an in vitro culture of immune cells. As you well know, the intestine has a very complex microbiological makeup - there are myriads of different types of microorganisms in the gut, and a subset of these microorganisms are pathogens or potential pathogens. Other individual bacterial species would be expected to also be capable of eliciting production of proinflammatory cytokines if they were studied in the same way - if they were introduced singly to in vitro cultures of immune cells within a similar experimental paradigm to that used by the authors in the study you cited. The focus of the study on klebsiella is because this is the particular pathogenic organism the authors used, not because it would be the only organism that would be capable of eliciting production of proinflammatory cytokines by immune cells.

More on the complexity of the microbial world present in the gut:
http://www.cell.com/content/article/fulltext?uid=PIIS0092867406001929

Evelyn,
My point was that due to success of TNF alpha inhibition the focus in AS research is getting more and more to the gut and not to the abnormal intrinsic capabilities of HLA-B27 for misfolding or similar explanations. To be honest I did a google yesterday with a few components like T-cell TNF etc and NOT with Klebsiella and was very surprised to see Klebsiella pop up as the first one in the list. That I choose to show it is because it shows that bacteria are able to trigger the same immune cells that are responsible for fuelling our inflammatory processses being the same immune cells that are inhibited by TNF alpha blocking. Another reason is that it makes a nice bridge between the sometimes opposing views and discussions here on these forums. In my view it could very well be that the success of TNF alpha inhibition and the success at least some of us have with diet have the same ground. If another pathogenic organism has the same effect on TNF alpha production that is no problem for me as this other bacterium will also respond to changes in his environment due to diet, antibiotics or probiotics.
I do by the way realise that the above could only explain part of the pathogenesis of AS, though it also could explain the positive effects and the problems having results when trying to change the indeed complex intestinal flora.
Best regards,
Gerard

Gerard, I've only just seen this now. I find myself particularly unwilling to get into a second debate this week. However, just because one author on a study has made shown a bias does not mean that all of them do. You cannot make that assumption. How many production teams have I worked on on which one of my team members has been an as$. Doesn't mean everyone on the team is an as$ and it certainly does not mean the the show being produced is going to be any less artistically valid. It just means that one teammate is an as$. Same with any research study. I rather doubt that everyone involved in a study believes exactly the same things in the same way. That would be counter to any good scientific research. It is the differences that create a more rich and thorough piece of research.

Again, you can no more colour the other authors of the study with the same paint because of the comments of one of them than you can make the statement that all of Dr. Enbringer's research is slanted because he believes the kleb p. related pathology in AS. And that is an easy assumption to make, but to do so is to invalidate every piece of his research. I certainly do not have the hubris to do that, being a lowly pleb in the grand AS scheme of things.

We also know that any one of us here does have an agenda - that being what he or she believes in any given instance. It would be very easy to say that John only posts things that agree with Dr. Enbringer and Evelyn only posts things that disagree with Dr. Enbringer. It would be very easy, but it would be untrue and unfair.

The study that I posted states only that there was no link found in the family studies that were done - from sibling to sibling. It certainly wasn't negating the entire theory. However, the accusation has been made that the research was skewed against kleb because of [insert spurious excuse here]. But research is only as skewed as our own points of view are when it comes to studying and reading the results of the research. If you firmly believe that kleb is the root cause of AS, then you're going to doubt the research. If you believe that the root cause of AS has yet to be determined, you'll be more inclined to accept the research as one more piece of a rather large puzzle.

Anyway, enough for now.

Hugs,

Dear Gerard, your note adds another area where I believe you and I could find some common ground: the intestinal flora is indeed complex, and alteration of diet could affect carriage of other pathogenic or potentially pathogenic organisms within that complex flora.

The same would hold true for use of antibiotics or introduction of probiotics: these could affect carriage of a variety of pathogens or potential pathogens within the complex flora of the gut.

Additionally gut inflammation and loss of epithelial integrity within the gut could provide exposure and loss of tolerance to food antigens that are not necessarily microbial in origin. A change in diet might potentially affect the immune response by providing a greater or lesser degree of exposure to food-derived antigens. Such a mechanism is in play in gluten enteropathy/celiac disease, and it is notable that there is a link between gluten sensitivity and arthritis.

To my understanding, the link between gut inflammation and the potential to develop AS/spondyloarthropathy is pretty broadly accepted, even though consensus on pathogenic mechanisms remains incomplete.
see:
http://ard.bmjjournals.com/cgi/content/abstract/ard.2005.047738v1

Hi Kat,

Quote:

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just because one author on a study has made shown a bias does not mean that all of them do

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You're right. Wished you didn't used the following metaphore(s) though, metaphores always blurr a discussion.

You're right in that is does not follow from it. Chances are however that if two authors publish 8 articles in three years together, all on different aspect of Ankylosing Spondylitis that they do share the same opinion on other closely related AS matters. The main reason however why I mentioned the "junk science" example is that having an agenda as you call it is not something that is exclusive for these forums.

My real problem with the article is that it has an highly improbable outcome. To show this I did a search on pubmed with three components: Antibody, Klebsiella and Ankylosing. For the last fifteen years I counted the researchers and research groups that were able to find an immune response to klebsiella in AS patients and those who didn't. (someone has to do the dirty job some time)
I got 59 results from which I skipped 9 because they were reviews or measured antibody response in faeces. From the remaining 50 there were 44 researches able to detect a higher immune response and 6 not. From those 6 there were three from the Feltkamp Sprenkels group which I discussed above and who later do were able to detect the immune response when they learned how to do it properly. So actually in the last 15 years there are only two researches from 1992 from two research groups that have a comparable outcome to the one you cited and 10 research groups and 44 researches that have another outcome.

I sm not objective and the above method is very crude but I do try as this whole thread shows to be as objective as possible. Otherwise the Evelyn's and JCwinny's and even Jeanna's of this site would wash my ears.

The above is by the way not to be interpreted as if the molecular mimicry theory that some have derived from it has the same amount of approval in scientific literature. Certainly not. The reaction to Klebsiella could for instance also be a side effect to an impaired immune reaction in the gut and some authors have suggested that. If you read my other reactions in this thread you will also note that to me the cause of AS is also unknown. But if you want to know my agenda it is this:

First come the three points I mentioned in my reaction to Jeanna.
Secondly I believe in a strong role for the immune system of the gut and gut inflammation as the driving force for AS. That inflammation is normally subclinical so you or me or even the doctor won't notice it unless specific research is done.
Thirdly I will react when someone says there is no proof for a role for Klebsiella. As my score list above shows there is ample evidence for a role for Klebsiella be it possibly along the sideline.

Up to know all working remedies against AS are in line with the above. Sulfasalazine, diet but especially TNF alpha inhibition which for instance works as good for Crohn's as for AS.
I could show the weak points in the conclusions of the Inman research and I will if someone would ask that. For now I think this reaction is really more then long enough. Kat please do stretch the leg now and then when reading this and a hug to you too.
Gerard

Hi there, thanks for clarifying. As an artist, I find it easier to analogize from an artistic viewpoint; hence, my specific analogy. I admire your tenacity in doing the searches at PubMed. These days I have neither the time nor the energy to do the indepth research I would like to do.

For the moment, I am content to accept what you say. And I certainly do not outright deny an involvement of kleb p in AS. I do, however, maintain that it is not necessarily true in all cases. I'm stubborn that way. Perhaps, one day, a kleb p test will be done on all potential AS cases and the results used in the same way as the HLA-B27 test - a positive result is a good indicator of AS, but a negative one does not necessarily rule out AS when the other symptoms are clearly AS related. However, I have a feeling that we are still a long way from that.

Consider my leg well stretched and my foot up (it's been propped on my hard drive while I type).

Hugs,

Hi Kat,
By reading your response I just have to know if you indeed read the latest Ebringer/Finnish research in which he suggested to use the antibody response to a particular Klebsiella peptide (piece of a protein) as a diagnostic tool. If not you have more then only the artistic talents and should become a researcher yourself, if you did you're mostly right in your conclusions except that I don't rule out that by that time we know so much more about AS that we don't consider it to be one disease any more.
Gerard

Truth be told, Gerald, I don't remember if I read it right now. I try to read research that's posted here, but sometimes by the time I'm done I feel as tho someone has presented me with the calculations for pi or E=Mc2 and asked me to present a brief on them!! In short, my eyes and head are swimming in terminology that I understand only sporadically at best and I'm like a dolphin in the middle of the Sahara.

We'll see what the future brings with regard to this. In a way, I do agree that AS is more than one disease. But the way I think of it is more in terms of a saying by Confucious (I think it was Confucious). There are as many philosophies (types of AS) as there are people in the world.

With the advent of genetic research and our growing knowledge of DNA, the ideal of treatment tailored for the individual is in our future. In the meantime...

Anyway, I've been trying to finish this post for two hours now and it's 5:20, so I'm going home.

Hugs,

AS; so it is polyphiloprogenitive? So many theories, even more words

They sell Polyfilla in our DIY stores to fill up the voids