Immune Process in #Gluten Disorders

Here is an interesting study published in Nature recently where the researchers tried to see what differences there were in the immunological disease processes in people with coeliac disease and non-coeliac gluten sensitivity.

Mucosal Cytokine Response After Short-Term Gluten Challenge in Celiac Disease and Non-Celiac Gluten Sensitivity

It’s believed that the two processes are very different and I have read much that suggests CD is one type of immunological response, whereas NCGS is thought to be a different type. I guess that’s what the researchers were looking at.

Basically, the abstract is a bit technical but they did find some similarities and some differences. Here is the conclusion:

CD patients mounted a concomitant innate and adaptive immune response to gluten challenge. NCGS patients had increased density of intraepithelial CD3+ T cells before challenge compared with disease controls and increased IFN-γ mRNA after challenge. Our results warrant further search for the pathogenic mechanisms for NCGS.

So, what the heck does that mean? I can’t promise to understand it totally as I am far from an immunologist!, but let’s start with what interferons (IFNs) are. Here’s a bit from Wikipedia; I’ve left all the links in case you want to look things up:

Interferons (IFNs) are proteins made and released by host cells in response to the presence of pathogens such as virusesbacteriaparasites or tumor cells. They allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.

IFNs belong to the large class of glycoproteins known as cytokines. Interferons are named after their ability to “interfere” with viral replication within host cells. IFNs have other functions: they activate immune cells, such as natural killer cells and macrophages; they increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes; and they increase the ability of uninfected host cells to resist new infection by virus. Certain symptoms, such as aching muscles and fever, are related to the production of IFNs during infection.

The researchers found that coeliacs had high alpha and gamma types, whereas the NCGSs had just high gamma, so there does appear to be a difference. I reckon this comes down to the fact that CD is the end-result full-blown inflammatory and auto-immune response whereas NCGS is the fore-runner gluten disorder that can lead ultimately to auto-immune or inflammatory diseases anywhere in the body depending where the target tissue or gland is. That is sheer guesswork, but I reckon that’s what we’re looking at from all the stuff I’ve read.

Let’s learn a bit more about the gamma type:

IFN-γ, or type II interferon, is a cytokine that is critical for innate and adaptive immunity against viral and intracellular bacterial infections and for tumor control. IFN-γ is an important activator of macrophages.

Aberrant IFN-γ (gamma) expression is associated with a number of autoinflammatory and autoimmune diseases. The importance of IFN-γ in the immune system stems in part from its ability to inhibit viral replication directly, and most importantly from its immunostimulatory and immunomodulatory effects. IFN-γ is produced predominantly by natural killer (NK) and natural killer T (NKT) cells as part of the innate immune response, and by CD4 Th1 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops.[5][6]

So, it is specifically seen in auto-immune and inflammatory disorders and is part of the body’s mechanism of controlling the development of those from what I understand of it. Note, too, that the IFNs, especially gamma, increases the immune reaction in antigen-specific immunity (ie. allergy/sensitivity).

Interesting. Now, let’s look at the increase seen in NCGSs of IELs (intraepithelial cells). I have often said that one of the first indicators of a gluten disorder could be high IELs. Sadly, though, they are difficult to count and path labs don’t often do it. I have had people ask for an IEL count when they are having a coeliac biopsy done because certain immunologists believe that a high IEL count can come long before the auto-immune villi damage.

Intraepithelial lymphocytes (IEL) are lymphocytes found in the epithelial layer of mammalian mucosal linings, such as the gastrointestinal (GI) tract and reproductive tract…. Upon encountering antigens, they immediately release cytokines and cause killing of infected target cells. In the GI tract, they are components of gut-associated lymphoid tissue (GALT).[1]

An elevated IEL population, as determined by biopsy, typically indicates ongoing inflammation within the mucosa. In diseases such as coeliac sprue, IEL elevation throughout the small intestine is one of many specific markers.[2]

IEL help preserve the integrity of damaged epithelial surfaces by providing the localized delivery of an epithelial cell growth factor. http://www.pnas.org/content/99/22/14338.full.pdf

In other words, the mucosal integrity (the barrier) and the mucosal immunity is affected by the level of IELs. A high level of them indicates some form of antigenic immune response – a reaction causing inflammation as I see it.

So, to summarise, there IS a disease process going on in NCGS which is different to coeliac disease. From what I can make of it, NCGS seems to be showing the start of the inflammatory gluten-reactive process with the high IELs and the higher IFN gamma. Could this be that the body is trying to keep control of the process before it develops into a full blown auto-immune disease like coeliac disease (or many others,) which then itself shows in even higher levels of the associated IFNs and cytokines being released?

I don’t know, but I look forward to this burgeoning area of science helping us find out what exactly is going on in NCGS.

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