Tag Archives: celiac disease treatment

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Interleukin-15 and Celiac Disease

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.

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New Year and New Celiac Info…

Happy New Year to all of you!

This post will focus on updated information about adult celiac disease that was presented at the Celiac Disease preceptorship that I attended at the University of Chicago in December 2014. Prior to the hustle and bustle of the holidays I was able to write a bit about what I learned about pediatric celiac disease (see link). I hope to share more information from the preceptorship in upcoming months, as time allows…

Dr. Carol Semrad, a celiac specialist from the Celiac Disease Center at the University of Chicago, gave a presentation entitled “Celiac Disease: The Adult Perspective” on December 4th. Here are some of the “highlights” from her excellent and comprehensive lecture.

75% of patients with celiac disease are diagnosed during the adult years. Many have only mild, intermittent gastrointestinal (GI) symptoms that they may think are “normal.”  Many adults are actually overweight/obese at the time of diagnosis. Others may have other problems (with either mild or absent GI symptoms) such as low bone mineral density, iron deficiency anemia, and hepatitis.

Celiac disease can present in 4 different ways:

1. Classical: diarrhea, gas/bloating, and weight loss
2. Atypical: fatigue, constipation, anemia, osteoporosis, dermatitis herpetiformis (rash), neuropathy, infertility, etc.
3. Asymptomatic: No symptoms, but positive celiac antibodies and an abnomal small bowel biopsy
4. Potential (latent): No symptoms, positive celiac antibodies but normal small bowel biopsy

The incidence of classical celiac disease is 1:4500, but the incidence of atypical, asymptomatic, and latent is 1:133. Celiac disease is not a rare disease like so many of us were taught during medical school.

The duodenal biopsy remains important for celiac disease diagnosis in adults and must be performed prior to a patient starting on a gluten-free diet. As discussed elsewhere during the conference, a “gluten challenge” in adults consists of eating at least 1/2 slice of bread for 2 weeks prior to a small bowel biopsy (and 6 weeks prior to celiac blood antibody testing).

Although villous blunting is the hallmark of celiac disease on small bowel biopsy, there are other diseases that can also cause villous blunting, which include tropical sprue, infections (Giardia, Cryptosporidia), Crohn’s Disease, small bowel bacterial overgrowth, olemsartan enteropathy, autoimmune enteropathy, and Graft v. Host Disease.  Villous recovery will occur on the gluten-free diet in celiac disease only (this can be used to differentiate celiac disease from the other causes of villous blunting).

Dr. Semrad recommended that patients with any of the following problems be tested for celiac with a duodenal biopsy:

-Diarrhea with weight loss
-Unexplained iron deficiency anemia
-Early osteoporosis
-Neuropathy or ataxia
-Positive celiac antibody tests prior to going on the GF diet

“High-Risk” patients who should have screening celiac antibody tests performed include those who have any of the following:

-First degree relatives of those with celiac (parents, siblings, and children)
-Type 1 diabetes
-Autoimmune thyroid disease
-Irritable Bowel Syndrome
-Asthma
-Multiple Sclerosis
-Primary Biliary Cirrhosis
-Down, Turner, and William’s syndromes

Treatment for celiac disease should include all of the following:
1. Life-long, strict gluten-free diet, including consultation with a dietician who is knowledgable about celiac disease
2. Lactose-free diet to start
3. Daily multivitamin and calcium
4. Folic acid for all women of child-bearing age

Patients with newly diagnosed celiac disease should follow-up with their physician and dietician at 3-6 months, and then every 1-2 years. Celiac antibodies should be retested after 3-12 months on the GF diet. Despite this, only 44% of newly diagnosed celiacs in the U.S. follow-up with their physicians, and only 3% have any follow-up with a dietician!

80% of patients with celiac disease will start to have improvement within 2 weeks of starting the GF diet. 20% will not have improvement at the 6 month mark and will be ultimately be diagnosed with nonresponsive celiac disease. Ongoing gluten ingestion is the most common cause of nonresponsive celiac disease. I’ll discuss both nonresponsive and refractory celiac disease in more detail in an upcoming post.  The bottom line is that if one continues to have symptoms after going on the GF diet, that follow-up is necessary.

Thank you for reading, and as always, please feel free to comment, ask questions, etc. Also, as an aside, please check out the January/February 2015 issue of Gluten-Free Living Magazine. I am featured in Susan Cohen’s article, “It’s Routine,” along with some other really cool celiac advocates including Dr. Fasano.