Wednesday, February 27, 2008

Gluten and NK cells (forget the antibodies)

I just thought I'd stick this down as it's minor and it will get forgotten if I don't say something. There are grades/types of inflammatory bowel disease. The really easy one to treat is coeliac disease, where gluten avoidance is all that is required. There are also a host of problems which are responsive to gluten avoidance which do not come up positive on antibody test or have "typical" coeliac gut biopsy results.

I stumbled across this paper which grabbed me because my wife works with Natural Killer (NK) cells and has pointed out their relevance to surviving diseases before antibodies kick in. I was lucky to get the full text.

This is from the introduction, before it discusses coeliac disease, which is the second disease it covers (rheumatoid arthritis is the first):

"MIC A/B are stress-induced molecules acting as danger signals to alert NK cells and CD8 T lymphocytes through engagement of the NKG2D activating receptor [2]. At variance with classical MHC class I molecules, MIC are specialized for reporting stress without the requirement for peptide (or other ligand) binding and can direct NK and T cells to kill transformed or infected cells."

This translates as:

Gluten stresses your gut cells. They scream on the molecular level. NK cells cells get in there and put them out of their misery. This is (auto) immunity. It does NOT REQUIRE antibody production.


Antibody production appears to be an add on to the immune system, a memory storage facility for preventing future re infection with a previous encountered bug. The acute survival of an infection, like influenza, relies on the innate immune system, based around NK cells. If you had to wait 10 days for your lymphocytes to get around to antibody production before you recovered, all viruses would be lethal. NK cells are non specific and use molecules like MIC as markers that something is seriously wrong with a cell and it's time to get killin'. MIC is a like a large target sign painted on a cell and NK cells are equipped an AK47 looking for that target. Usually a cell expressing MIC is infected, but gluten appears to do as much "stressing" as a viral infection.


Gluten reactions do not need antibody production. It is perfectly possible to have serious on going gut damage without a positive antibody test. Statistically it is quite probable that you WILL get a positve antibody test. There is so much damage going in that battlefield which is your gut under the influence of gluten that there is a trauma "soup". All you need is for an "antigen presenting cell" (APC) to collect some gluten from this soup, give it to your lymphocytes and tell them "we want this stuff recognised by an antibody, get producing". Of course the APC may pick up tissue transaminase, endomysial protein or any of a host of other proteins to push at the lymphocytes (which make the antibodies). But there is a chance you may not get either gluten or transaminase etc presented (ie no antibodies in our current lab tests), so you continue with "psychosomatic" gut problems or get labeled as inflammatory bowel disease, which is not regarded as gluten responsive. Severe IBD requires more than gluten avoidance but this basic step is probably essential.

Antibodies are a consequence, and an amplifier, of gluten toxicity, not a cause. That's intrinsic to gluten, MIC and NK cells. What brought this on?

Speculation time.

Did I have psoriasis or Dermatitis Herpetiformis (essentially coeliac disease of the skin)?

Answer: Maybe it's the same parallel as gut problems. WGA certainly gets in to the systemic circulation. I think it's a reasonable assumption gluten does too. It will be landing on vascular and/or dermal cells in the skin. Gluten induced stress here results in MIC expression. NK cells have that AK47, an itchy trigger finger and are seriously looking for MIC. Sometimes there is antibody production, sometimes there isn't. This could easily be the result of receptor subtypes (genetic) on your antigen presenting cells. Different labels, different lab results (if it ever gets that far) but a similar approach is needed. Perhaps there are a host of immune mediated problems triggered by gluten that are not antibody producing.



Anonymous said...

Hi Peter:

Great blog, which I love and wouldn't miss a single post.

This reminds me of something you talked about in a recent post as to the use of Omeprozole and other pump inhibitors.

I've been on one or the others of those for some years. Having begun a workout program, and then low-to-no carb last October, I was able to get off a Flonnaise like nasal spray for sinus allergies I've been on for years, and I also quit taking Levothroid (125 mcg/day) around the holidays. I'd been on this for hypo-thyroid, a test showing a slightly abnormal thyroid producing hormone, or something. Interestingly, getting off the levothroid is the point at which my weight really began dropping. results here:

Anyway, long story short is that I tried to go off the Omeprozole but had to go back on. The heartburn was just too bothersome, even with almost no carbs. However, I do consume alcohol (single malt scotch: a weakness).

Any suggestions off hand? For the time being I'm taking the whole dose and have no heartburn ever, but I'd really like to get off it and wondered if you've had any ideas about what I might do.

Peter said...

Hi Richard,

I see from your blog that you eat paleo. I just assume you are grain free. I've no idea how gluten triggers acid reflux but that was the primary problem my wife was suffering from before LC. In the early days, if she lapsed, that was the primary problem to come back. She ate Atkins induction, completely gluten free.

You probably know that all of the LC writers consider acid reflux to be the easiest of the GI conditions to manage, which must make the omeprazole a bit galling.

OK, assuming you're gluten free, this is what happened with my wife on relapses. Just going LC strictly was not enough. After about a week or two of non resolution (still omeprazole free) we did something extra. The first time was an accident, it was very early in LC and she developed routine thrush, which had been a minor recurrent problem pre LC. It tended to flare when she lapsed. Yeasts eat sugar, LC lapses cause hyperglycaemia. Taking a single fluconazole 150mg capsule sorted the thrush and gut out on the same day. We were amazed. She did this for about two more gut only episodes in the aftermath of a carb binge or gluten exposure. It worked. Not needed it after that first year or so.

I thought this was pretty out on a limb. There is a great deal of rubbish on the net about generalised candidiasis. I'd also point out that clinical experience is no guide to efficacy. Might easily be coincidence.

Then I found this paper.

Klebsiella is a bacterium associated with IBS and systemic problems like anterior uveitis and ankylosing spondylitis. It eats fiber/starch. It is intimately associated with yeasts in the gut, acting as an adhesion factor for the yeast. As no one seems to know why LC improves acid reflux and the gut microbiota undoubtedly influence body function distant to the gut, I see no intrinsic problem with believing that yeasts in the gut might influence acid reflux. In the UK fluconazole is available OTC.

That's what we did/found. We're not doctors. This is not advice!

Don't forget that you're might well be B12 deficient on omeprazole (warns re this on data sheet, no one told us) and that it doubles the level of gastrin in your blood. There are concerns about this latter effect.

Oh, single malts! I love them, my joints hate them. There should be no gluten in the distillate, but how do they get that beautiful golden colour? Oak barrels, yes. A trace of barley malt too perhaps? Dunno, but I'd switch. A wee voddy may taste of nothing, but it has no congers and absolutely no gluten. Boring, but trying it for a month is worth a go.


Anonymous said...

Thank you Peter. Now I'll have to get busy and digest all this, then maybe some experiments of my own.

Anonymous said...

I'm with Peter. The safest alcohols are probably vodka and gin. They're less likely to cause hang-overs the more they're distilled and filtered to remove toxins/impurities. A word of warning: eating alcohol with any high-PUFA oils, including fish fat, seems like a very bad idea.

"...Polyunsaturated fat (vegetable or fish oil) is known as a critical nutritional factor for induction of experimental ALD and feeding saturated fat (beef fat) results in remarkable prevention of or accelerated recovery from experimental ALD. Indeed, epidemiological studies support these observations by revealing a positive correlation of the incidence of cirrhosis in various countries with consumption per capita of polyunsaturated fatty acids, particularly linoleic acid and an inverse correlation with saturated fat. It is postulated that polyunsaturated fat accentuates alcohol-induced oxidative injury via its synergistic effect on induction of microsomal ethanol-oxidizing enzymes (e.g., cytochrome P4502E1, CYP2E1)." (second paragraph)

I think alcohol would be safest if eaten with beef / lamb fat, butter, cheese, cocoa butter, or 85% cocoa bar, coconut oil, mac nut oil, dry roasted macadamias, foie gras, etc. Those are very low in PUFAs.

Adam Steer said...

Hi Peter,

I've been hearing about this blog but have not, until now, had the chance to take a look. Great job!

Upon reading this post, a long standing question of mine resurfaced. Do you have an opinion on gluten's effect on auto-immune disease. My wife suffers from rheumatoid arthritis. I'm pretty much a low-carb guy, but my wife does not really buy into it. I'm sure that gluten does not help, but would love to be pointed to any substantiation which might help my case. ;-)


Peter said...

Hi Adam,

Just had two days work so not much time to blog. RA has a number of factors involved, gluten or wga are in there high up the list, so is insulin and hyperglycaemia. There's a full post or two there but absolute gluten (possibly all grains) elimination cobined with LC is a good starting point. There are a few other factors but they probably get addressed indirectly by LC/grain free.


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