the patient celiac

Interleukin-15 and Celiac Disease

14 comments November 27, 2015

IL-15 is an important cytokine (immune system protein) involved in celiac disease. In those of us with celiac, ingestion of gluten triggers the release of IL-15 by cells in the lining of our small intestines. IL-15 stimulates the production of intraepithelial lymphocytes (IELs) which are unique immune cells found in the lining of the small intestine—these are often seen on our intestinal biopsies when we are first diagnosed with celiac disease.

Based on the work of Dr. Jabri and colleagues at the University of Chicago, we know that IL-15 has 4 major roles in celiac disease. It is involved in all of the following:

  1. Loss of tolerance to gluten.
  2. Loss of immune system regulation.
  3. Epithelial cell destruction in the small intestines.
  4. Promotion of the growth of aberrant, or abnormal, IELs.
IL-15 is involved in the development of both non-responsive celiac disease and refractory celiac disease. Non-responsive celiac disease (NRCD) is diagnosed when one has persistent symptoms, elevated celiac antibodies (i.e. TTG-IgA) and/or small intestinal damage after at least 6 to 12 months on the GF diet. Although most cases of NRCD are due to accidental ingestion of gluten, a small percentage of cases are due to refractory celiac disease, which involves persistent symptoms, antibodies and intestinal damage in the presence of abnormal IELs. Refractory celiac disease, which can associated with the development of lymphoma, is difficult to treat as it does not respond to the gluten-free diet.

AMG-714 is a monoclonal antibody that blocks IL-15. I was given the opportunity last month to interview Dr. Francisco Leon, MD, PhD, the CEO and CMO of Celimmune, a company that is investigating the use of AMG-714 as a treatment for celiac disease. According to Dr. Leon, Celimmune has two Phase IIb clinical trials of AMG-714 in the works. The first, which will take place in European centers, will be targeting subjects with non-responsive celiac disease. It will involve subcutaneous injections of AMG 714 every 2 to 4 weeks. The second trial, which will be centered in the U.S. (New York and San Diego), will involve the intravenous dosing of AMG 714 to subjects with refractory celiac disease. They aim to recruit 24 subjects with refractory celiac disease, starting in March 2016, for the U.S. trial. Please see clinicaltrials.gov in upcoming months for more information on study design, enrollment criteria, etc.

The bottom line, from my discussion with Dr. Leon, is that help is on the way for those with persistent symptoms despite being on strict gluten free diets and that we will soon be able to tailor our management of celiac disease to our specific needs and lifestyles.

For more information on IL-15, AMG 714, and other celiac therapeutic agents in development, please see Dr. Leon’s recent article (reference #3 below).

References:

Valérie Abadie and Bana Jabri. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev. 2014 Jul; 260(1): 221–234.

Rubio-Tapia, A, Hill, ID, Kelly, CP, et al. American College of Gastroenterology. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol. 2013; 108: 656-76.

Leon, F and Llewellyn, B. Experimental therapeutics for celiac disease and refractory celiac disease. Drug Discovery World. Spring 2015. 73-78.

Comments
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7/19/2016 5:10:37 PM
Jess
In reply to Spiffy.
Hi Spiffy,
You’re welcome. I never really know if/when people are checking out my site anymore because I’ve stopped looking through the analytics. So I really appreciate your feedback and I hope your RA factor goes down too :)
7/19/2016 5:09:49 PM
Spiffy
Oh, my goodness. I took the time to read some of your earlier posts. We actually had a lot of the same symptoms! Oh, how I am hoping my ra factor will go down! You are such a source of inspiration. Thank you so much for taking the time to create your website!
7/19/2016 5:09:20 PM
Spiffy
I am so happy to have found your website. Your story is incredible. You are so fortunate that as sick as you were your body did not start another autoimmune process. All of my life, I have suffered from constipation. The only exception was when I took the pill our first two years of marriage. That caused quite the opposite effect. I had a colonoscopy. Nothing found. My only complaint when I went to the doctor was constipation. No one got that excited. Exactly a year after my dad died died I began to get transient rashes and hair loss. A few months later came massive fatigue, tight neck, weakness, etc. major sleep disturbances. Positive IGM for Lyme through Igenix to include bands 31 and 34. Sometimes I would wake up with a completely numb arm. I lost 16 pounds. I am 5’10 and thin anyway. Functional medicine doc finally did IGG allergy testing. I was allergic to wheat, gluten, egg, and dairy among others. My gluten level was not that high, but I had been gluten free for 3 weeks before. My neutrophils were always a little high and my lymphs a little low. The really sad news. I developed an ra factor of 71. It is now down to 36 as of Aug. 2015 hopefully because of diet changes, minocyclene, and supplements. I am compound heterozygous for MTHFR and am HLA DR4/DR13 and DQ8/DQ6 positive. Strangely enough, no one in my family has ever had ra or celiac. My rheumy says I do not have ra, but I am not going to sit around and wait for more symptoms. I am trying to be proactive. My dad’s three surgeries he had were a tonsillectomy, hernia repair, and appendectomy. An article I read said that these were the three surgeries that most undiagnosed celiacs have. Interesting. He also had primary pulmonary hypertension. No one knew why. I will never know if I have Celiac. There is no way I would get back on it. I do feel much better without it. My sinuses are completely clear for the first time I can remember. My acne is gone. I wish I could have been the type to get sick and get better! My message is this. Do not accept symptoms that are not normal. I wish a doctor had said even ten years ago….let’s figure this out. If I had given up gluten earlier, I would never have developed an ra factor. I will always believe that. I am hoping I will be one of those who auto antibodies will normalize in time. I am very disciplined with my diet. Anyway, I just wanted to share my story in case I can help someone else. I would appreciate hearing from you…not for medical advice…just your friendly thoughts would be much appreciated.
7/19/2016 5:08:16 PM
monique
thanks for the info! you are always so on top of the latest research. it is nice to know there may be other options and more research ongoing with regards to this autoimmune disease. i feel like there is so much more about celiac that will come out in the future of medicine. at least i hope so!
7/19/2016 5:07:41 PM
Vik
In reply to Jess.
Yes, in fact, the notifications started coming within the last few posts. Before that, they quit coming for so long that I actually thought you were on total hiatus.
7/19/2016 5:07:06 PM
Jess
In reply to Vik.
Hi Vik! You’re welcome. There should be more to come in upcoming months. Are you actually getting notifications of my posts again? I’m asking because it’s been an ongoing problem.
Jess
7/19/2016 5:06:43 PM
Jess
In reply to Karen.
You’re welcome Karen. I am continually surprised by how many are angered by the thought of there being a medication to help treat Celiac. For some of us, following the GF diet works great–our symptoms go away and our antibodies and biopsies improve, and it’s the perfect treatment for us.
But for others (40-50% of celiacs, depending on the study quoted) the GF diet is not enough. I can tell you that for other medical conditions, that a 40-50% failure rate for a treatment would considered horrendous. That is why is it reassuring that we will soon have other options to treat this disease. They won’t be for everyone, but should make a huge difference for those who continue to suffer.
7/19/2016 5:06:26 PM
Jess
In reply to Lisa.
Thanks so much Lisa. The study should pop up on the clinicaltrials.gov website sometime in the late winter or early spring. I’ll also put a link to it on my FB page once it is up and running.
Jess
7/19/2016 5:06:03 PM
Jess
In reply to Kelli.
Thanks Kelli! While these treatments will not be for everyone, they should lead to an improved quality of life for some who continue to have symptoms even while being as strictly GF as possible.
7/19/2016 5:04:18 PM
Vik
Hi Jess, I always appreciate your sharing of research and making it understandable for non-physician types!
7/19/2016 5:03:57 PM
Karen
Thank you so much for providing this kind of information! It is helpful to know that research continues for difficult cases.
7/19/2016 5:03:36 PM
Lisa
I know someone in San Diego with endoscopic biopsies from multiple post gluten removal that they may consider for this trial. Will let her know 😉
7/19/2016 5:03:09 PM
Kelli
Fingers crossed!
7/19/2016 5:02:39 PM
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