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Crohn's Disease Forum » Books, Multimedia, Research & News » Elevated calprotectin? - You could have a mycobacterium infection


07-21-2017, 04:51 PM   #1
OleJ
 
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Elevated calprotectin? - You could have a mycobacterium infection

Many Crohn's patients, myself included, have always had elevated calprotectin levels more often than not.
As an example, here is a graph of my levels the past seven years:



I wondered what elevated calprotectin actually means?
There is growing evidence that mycobacterium paratuberculosis (MAP) is a trigger of some cases of CD and I recently tested positive for MAP. Is there a connection to calprotectin I wondered? The lab cultured live daughter cells, which are the type of bacteria the immune system picks up and reacts to (picture from my MAP test result report below):


Could it be that calprotectin elevates when the immune system detects MAP cells? So I did a search to see if there is a connection between mycobacterium infection and calprotectin.

Two studies came up:

The first study MRP8/14 [=calprotectin] induces autophagy to eliminate intracellular Mycobacterium bovis BCG. concludes (quote):
The present study revealed a novel role of MRP8/14 in the autophagy-mediated elimination of intracellular BCG by promoting ROS generation, which may provide a promising therapeutic target for tuberculosis and other intracellular bacterial infectious diseases.

(end quote)

What that means is calprotectin is released by the immune system to help kill the infected cells.

The second study:
Calprotectin (MRP8/14 protein complex) release during mycobacterial infection in vitro and in vivo. concludes (quote):
Human MRP8/14 significantly increased Mycobacterium tuberculosis H37Rv growth in liquid medium in a dose- and time-dependent manner. These findings suggest that MRP8/14 plays an important role in the immunopathogenesis of tuberculosis.
(end quote)

Even though MAP is a different subtype of mycobacterium than M.tuberculosis and M. bovis, it shares similarities with both, as described in the study Interaction between Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium subspecies paratuberculosis with the enteric glia and microglial cells.

I am more and more convinced that the mycobacteria we get from dairy cows (and possibly other sources) is harmful. I for one am through with dairy and minced meat as long as MAP is present in the food products. Including matured cheese and pasteurized milk - MAP survives both processes. Also, when a cow gets sick with MAP it is reportedly still slaughtered and the meat is sold.

Last edited by OleJ; 07-22-2017 at 12:25 AM.
07-22-2017, 07:27 AM   #2
JMC
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When you say you tested positive for MAP, what type of test was it (culture, monoclonal antibody, qPCR/IS900) and who performed it?
07-22-2017, 07:55 AM   #3
OleJ
 
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Hi JMC. It was positive by culture. I send two blood samples to Otakaro Pathways in New Zealand in May, and got the result back in the end of June.
07-22-2017, 08:51 AM   #4
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Hi JMC. It was positive by culture. I send two blood samples to Otakaro Pathways in New Zealand in May, and got the result back in the end of June.
I look forward to that culture method being published and independently validated as we really need a good MAP test. At the moment, as with some other MAP tests, I think you need to be sceptical about the results. With little or no information in the public domain about how this works (and I am very familiar with John Aitken and his lab) it is hard to convince the medical profession of the value of this result.
07-22-2017, 04:22 PM   #5
OleJ
 
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Very true JMC. I did read that a lab in Sydney validated the technique, but you are right we need proper publication and possibly FDA approval before it can become a gold standard test. I have read that John and his lab is in the process of publicising.
Yes, for the above reasons you could argue that it is to early to take John Aitkens test and act on the result. On the other hand, I don't see any reason not to act on it?

Last edited by OleJ; 07-22-2017 at 04:43 PM.
07-22-2017, 04:56 PM   #6
JMC
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Yes, for the above reasons you could argue that it is to early to take John Aitkens test and act on the result. On the other hand, I don't see any reason not to act on it?
The only course of action to take at the moment, would be to try the triple antibiotic therapy which is being trialled as RHB104 or something similar including rifampzin and metronidazole. If you are treatment naive for biologic therapies or have failed with other treatments, I cannot think of any reason not to have a go with this.

What I am in a little more concerned about, is people drawing definite conclusions or deriving a lot of hope from a test that has been much talked about for a number of years now, but still has not been published.
07-23-2017, 01:14 AM   #7
OleJ
 
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I agree that certainty should be reserved for research, diagnostics, and treatment regimens which have been verified by the relevant authorities.
Having said that, I do not see any problems in discussing and conveying information about research, diagnostics, and treatment regimens available, even though they have not yet been approved by the FDA. The more we know - the better decisions can we make.
For that reason I am very much interested in research that oppose the "MAP is a trigger of CD" hypothesis.
Note the may in the title of this thread - I am not being definitive, just putting forward a hypothesis and something to be aware of. I do think, however, there are grounds for taking Okakara Pathways seriously, and assume they are doing solid work.

In the most recent news letter from humanpara.org, John Aitken writes:
"The last year has been particularly busy and productive for us. As a result of the Philadelphia conference we have formed some good collaborations with university researchers in both the USA, Canada and the UK, in addition to our long-standing research relationship with the Centre for Digestive Disease in Sydney. The CDD is the centre of the known universe, in terms of novel ideas and experiments. We have finished our stage one research work on the behaviour of the organism in cultures. This work, supported by patients who sent us samples, has enabled us to design a medium capable of promoting growth via established biochemical pathways. What this means is that we have “tamed the beast” and can now predict behaviour in different media.

Regarding measures to take against MAP infection, yes RHB-104 is an option, and I too wait in anticipation for their interim conclusions due in August.

But antibiotics it is not the only treatment option. For instance, the anti-mycobacterial effects of Methotrexate are well established. I am currently without any CD symptoms and in near clinical remission on methotrexate mono-therapy.

Also some research indicates that diet and exercise could maybe stimulate autophagy, which helps erradicate the infections. I know very little about this though.

Last edited by OleJ; 07-23-2017 at 01:30 AM.
07-23-2017, 05:12 AM   #8
JMC
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Also some research indicates that diet and exercise could maybe stimulate autophagy, which helps erradicate the infections. I know very little about this though.
Exercise, in my experience, definitely has a significant and positive impact, particularly if you have significant problems with fatigue. There are some research studies going on at present into whether this benefits Crohn's patients - I suspect the answer will be yes.

Vitamin D taken daily also is helpful (Thomas Borody talks about this). I have also had benefit from Glucosamine/Chondroitin and a few other supplements. Basically, you have to use the "officially approved" medications and experiment yourself with other things like diet, exercise, supplements, meditation to find what works for you.
07-23-2017, 07:35 AM   #9
OleJ
 
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JMC, thank you for the comment. I was not aware there is research going on into CD and exercise. I would be very interested in references.
07-23-2017, 11:19 AM   #10
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Here you go: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376686/
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