EPSTEIN-BARR VIRUS in MC and AUTOIMMUNITY!!

[Zizzle]

During the last year that my autoimmune skin rash was flaring, I had swollen lymph nodes in the back of my neck. They promptly disappeared when I started prednisone, but they were really starting to worry me. I wonder if they will swell again as I taper off.

[gluten]

Hi Zizzle, Since your post about EPV I have found some interesting sites. Just type in the titles . " Epstein-Barr Vitus as a Trigger of Autoimmune diseases " " Infections and autoimmune diseases" "Epstein-Barr virus-transformed lymphocytes produce monoclonal autoantibodies that react with antigens in multiple organs" "Infections and autoimmunity--friends or foe" " Infections and autoimmunity: a panorama" John

[Zizzle]

The evidence keeps mounting. This supports my theory that infection with mono as a teen, results in different outcomes that infection as a child. Now EBV is being tied to breast cancer!!:shock:

http://scienceblogs.com/aetiology/2013/ ... st-cancer/

However, the age at which EBV is contracted seems to play a role in the risk of developing breast cancer. Women in Western countries are at higher risk of developing breast cancer and tend to be infected with EBV during adolescence or young adulthood, whereas women from non-Western countries have a lower risk for developing breast cancer and tend be infected during infancy or early childhood.

[Zizzle]

I just posted this in another thread, but it reallly belongs here:

Does this study about Interleukin-15 levels and their resulting lack of suppression of T cells add to our collective knowledge about the factors leading to MC and celiac?

http://www.celiac.com/articles/23118/1/ ... Page1.html

Are researchers looking at drugs to suppress IL-15 specifically?

From Wikipedia:

This cytokine induces cell proliferation of natural killer cells; cells of the innate immune system whose principal role is to kill virally infected cells.

Notice the strange link to celiac and EPSTEIN BARR VIRUS!

Function

Interleukin 15 (IL-15) regulates T and natural killer (NK) cell activation and proliferation. Survival signals that maintain memory T cells in the absence of antigen are provided by IL-15. This cytokine is also implicated in NK cell development. In rodent lymphocytes, IL-15 prevents apoptosis by inducing an apoptosis inhibitor, BCL2L1/BCL-x(L).[6] In humans with celiac disease IL-15 similarly suppresses apoptosis in T-lymphocytes by inducing Bcl-2 and/or Bcl-xL.[14]
A hematopoietin receptor, the IL-15 receptor, that binds IL-15 propagates its function. Some subunits of the IL-15 receptor are shared in common with the receptor for a structurally related cytokine called interleukin 2 (IL-2) allowing both cytokines to compete for and negatively regulate each other's activity. CD8+ memory T cell number is controlled by a balance between IL-15 and IL-2. When IL-15 binds its receptor, JAK kinase, STAT3, STAT5, and STAT6 transcription factors are activated to elicit downstream signaling events.
Disease

Epstein-Barr virus
In humans with history of acute infectious mononucleosis (the syndrome associated with primary Epstein-Barr virus infection), IL-15R expressing lymphocytes are not detected--even 14 years after infection.[15]

Celiac disease
There have been recent studies suggesting that suppression of IL-15 may be a potential treatment for celiac disease and even presents the possibility of preventing its development. In one study with mice blocking IL-15 with an antibody led to the reversal of autoimmune intestinal damage.[16] In another study mice used were able to eat gluten without developing symptoms.[17]

Immunotherapy

Metastatic cancer
IL-15 has been shown to enhance the anti-tumor immunity of CD8+ T cells in pre-clinical models.[18][19] A phase I clinical trial to evaluate the safety, dosing, and anti-tumor efficacy of IL-15 in patients with metastatic melanoma and renal cell carcinoma (kidney cancer) has begun to enroll patients at the National Institutes of Health.[20]

[Zizzle]

Here's the original 2006 article referenced by Wikipedia:

http://bloodjournal.hematologylibrary.o ... t/108/1/11

EBV-associated mononucleosis leads to long-term global deficit in T-cell responsiveness to IL-15

In mice, interleukin-7 (IL-7) and IL-15 are involved in T-cell homeostasis and the maintenance of immunologic memory. Here, we follow virus-induced responses in infectious mononucleosis (IM) patients from primary Epstein-Barr virus (EBV) infection into long-term virus carriage, monitoring IL-7 and IL-15 receptor (IL-R) expression by antibody staining and cytokine responsiveness by STAT5 phosphorylation and in vitro proliferation. Expression of IL-7Rα was lost from all CD8+ T cells, including EBV epitope-specific populations, during acute IM. Thereafter, expression recovered quickly on total CD8+ cells but slowly and incompletely on EBV-specific memory cells. Expression of IL-15Rα was also lost in acute IM and remained undetectable thereafter not just on EBV-specific CD8+ populations but on the whole peripheral T- and natural killer (NK)-cell pool. This deficit, correlating with defective IL-15 responsiveness in vitro, was consistently observed in patients up to 14 years after IM but not in patients after cytomegalovirus (CMV)-associated mononucleosis, or in healthy EBV carriers with no history of IM, or in EBV-naive individuals. By permanently scarring the immune system, symptomatic primary EBV infection provides a unique cohort of patients through which to study the effects of impaired IL-15 signaling on human lymphocyte functions in vitro and in vivo. (Blood. 2006;108:11-18)

[tex]

Zizzle,

You may be interested in this related information about IL-15 from my book, from pages 192–193:

Interleukin-15 may interact with vitamin A to promote the loss of tolerance for gluten
Recent research has shown that a metabolite of vitamin A, retinoic acid, together with interleukin-15 (IL-15) in the intestines of patients with celiac disease, may be responsible for generating the inflammation that results in celiac disease.7 Since the problem does not occur if IL-15 is absent, it has been proposed that developing ways to block IL-15 may be an effective approach for preventing and treating gluten sensitivity. Like retinoic acid, isotretinoin is a first-generation retinoid, and it is the active ingredient in the product Accutane and other medications used in the treatment in acne, that have been associated with the development of inflammatory bowel disease. Obviously, this may have implications for both the prevention and treatment of microscopic colitis, as well.

This also implies that until a safe and effective way to block IL-15 is developed, if we take a vitamin A supplement, we should minimize the retinol form that is found in many vitamins. Instead, our vitamin A supplementation should be limited to the beta-carotene form, whenever possible. It appears that the esters of retinol may also be a problem.

The main component of palm oil is retinyl palmitate, which is an ester of retinol. Also, the terms "Retinyl acetate", "retinol acetate", and "vitamin A acetate", are all names for the same thing. They refer to the acetate ester of retinol, which apparently is ultimately converted to retinoic acid by the body. This conversion tends to occur whether the product is applied topically (to the skin) or ingested. That suggests that for anyone sensitive to gluten, the retinol that results from the conversion could combine with IL-15 to generate enteritis, (intestinal inflammation).

Tex

[Zizzle]

Thanks Tex, very interesting indeed. The fact that celiac and EBV/teenage mono share this same IL-15 dysfunction is strangely comforting to me. I think this may be my smoking gun. It would explain why I'm the first person in my entire extended family to get sick with anything before old age (I am the first person in my family to have mono). Before all this, I thought I had won the genetic lottery! I think it also may explain why I'm generally not THAT sick. Yes, my lymphocytes are running around unchecked, but all other systems are in fine shape and I feel good most of the time, not even fatigued. I've got the mildest form of Dermatomyositis so far, which I would rather refer to as "Lymphocytic Dermatitis" to be more accurate. That way I wouldn't have a daily reminder that my diagnosis is serious and sometimes fatal.

I hope there is research into IL-15 and antivirals for EBV. I doubt a vaccine would do me any good. I think it is no coincidence that this disease started with a post-partum flare. I believe the immune suppression of pregnancy allowed the EBV to reactivate just long enough to lose some tolerance to self, and that was that. I'm confident I wasn't gluten intolerant my whole life. Maybe after the Hep B injections (when mild IBS became apparent), maybe after my pregnancies, but I don't believe gluten is my root cause...just something that happened along the way.

I suppose I'll need to be vigilant for other EBV/mono-related diseases like lymphomas, breast cancer, etc. And I'll avoid synthetic Vitamin A like the plague!

[gluten]

Hi Zizzle, Today, I had a interesting talk with a genetic researcher. I ask her about EPV and it implications. The EPV virus is used to keep the cell lines alive in their research. If they did not use it they would die. So, my question is " Could the EPV do the same in the body" The researcher could not answer that question and would ask other researchers for the answer. Jon

[Zizzle]

Here's a fascinating (long) read about the search for answers (and viruses) in Chronic Fatigue Syndrome.

When Mikovits used the microarray to study CFS patients, she “saw all these infections—lots of chronic, active infections—cytomegalovirus, Epstein-Barr virus, human herpes six,” she says. It looked like an acquired immune deficiency syndrome, “like an AIDS patient,” with a weakened immune system enabling opportunistic infections to take root. The question was, why did they have chronic immune dysfunction?

http://discovermagazine.com/2013/march/ ... TZUnaI3vxA

[gluten]

Hi Zizzle, I read the article and found the comment interesting how they injected cell lines into a mouse to keep them alive. Jon

[tex]

Incidentally, Zizzle,

Speaking of viruses, have you ever read the old article (written almost 7 years ago, on his old website) written by DogtorJ, on the subject of the Ehlers Danlos syndrome? I don't know if he has written anything more recent about it, but he was apparently an early adapter in this area of study.

Ehlers Danlos Syndrome- Is it a Key to Our Understanding of Collagen Disorders?]

The same article is posted on his new website, but the text appears to be unchanged:

http://dogtorj.com/main-course/the-orig ... disorders/

Tex

[Stanz]

Your first link does't work, Wayne, but the second is priceless. I've run across him before in my research, thanks for the link.

[tex]

Hmmmm. That's weird. The link works fine for me. The article there is exactly the same as the other — the only difference is that the page is formatted completely differently.

Dr. Symes is an out-of-the-box thinker, which I like. Collagen is the connective tissue that holds our cells together, and CC is a connective tissue disease (at least, that's the marker that's used to diagnose it). And if CC is a connective tissue disease, then how could LC (or any of the other forms of MC) not also be a connective tissue disease?

Tex

[MBombardier]

Just FYI ~ I've been following this thread again because my 25yo son was just diagnosed with mono. I am in Dallas right now staying with him and his wife because she started having pre-term labor on Tuesday. I am mainly spending time with my 2-1/2yo grand-daughter while her mother is on total bed rest.

I talked a little bit with my DIL's mother today about the food intolerances in their family that they've been dealing with for many years. I wish I could get my son and his family to go at least gluten-free, but I have to have the patience to let them come to their own conclusions, I guess.

Anyway--I read on here about having mono in one's 20's, so I will be waiting to see what happens in my son's health, if his autoimmune issues manifest themselves. It's too bad, but it is what it is.

[Zizzle]

Interesting, from an article about mononucleosis in college students. More evidence that getting mono as a teen is much different than infection in childhood. Also seems to suggest that genetic/immune system factors in the victim may explain varying degrees of illness, and future complications.

Balfour and colleagues also found that the severity of illness seemed to be highest with very high Epstein-Barr virus load and high levels of CD8 cells, which form atypical lymphocytes that are characteristic of this disease.

the severity of illness seems to correlate with immune response. It is a vigorous immune response rather than the virus itself that causes illness, and we know this because very young children, for example, are rarely clinically symptomatic.

It should be noted that intermittent shedding could occur lifelong.

http://www.medscape.com/viewarticle/780810