Tag Archives: nonresponsive celiac disease

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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.

CeliAction Study Extension

I sincerely hope to be back to blogging soon. In the meantime I wanted to let you all know that the CeliAction Study has been extended through September 2014, so it is not too late to participate. All questions and comments on this post will receive responses from a CeliAction Study representative. I hope you are all having a great summer!  -Jess

celiactionaugust

Did you know there isn’t a single drug approved to treat celiac disease? Currently, attempting a gluten-free diet is the only option recommended by doctors, but a clinical research study called the CeliAction Study is researching if an investigational drug improves any symptoms of the disease.

You may qualify for the CeliAction Study if you:

  • Have been diagnosed with celiac disease by a healthcare professional
  • Are attempting to be on a gluten-free diet
  • Have experienced at least one moderate or severe symptom of celiac disease in the past month

If you participate in the CeliAction Study, you:

  • Will be able to maintain your current diet restrictions
  • Will be provided with study-related care at no cost
  • Do not need medical insurance to take part
  • May be compensated for time and travel
  • Will help advance medical research for celiac disease

To learn more about this research study and see if you qualify, visit www.CeliActionStudy.com
or call 1-855-3333-ACT.

The CeliAction Study

A significant percentage of patients with celiac disease continue to have gastrointestinal symptoms and/or small bowel inflammation while on the gluten-free diet. The Celiaction Study is recruiting subjects with celiac disease to test a medication that will help improve symptoms of celiac patients who are already on the gluten-free diet. Since this is a sponsored post, all questions will be answered by a CeliAction Study representative. Thank you!  -Jess

celiaction

Did you know there isn’t a single drug approved to treat celiac disease? Currently, attempting a gluten-free diet is the only option recommended by doctors, but a clinical research study called the CeliAction Study is researching if an investigational drug improves any symptoms of the disease.

You may qualify for the CeliAction Study if you:

  • Have been diagnosed with celiac disease by a healthcare professional
  • Are attempting to be on a gluten-free diet
  • Have experienced at least one moderate or severe symptom of celiac disease in the past month

If you participate in the CeliAction Study, you:

  • Will be able to maintain your current diet restrictions
  • Will be provided with study-related care at no cost
  • Do not need medical insurance to take part
  • May be compensated for time and travel
  • Will help advance medical research for celiac disease

To learn more about this research study and see if you qualify, visit www.CeliActionStudy.com
or call 1-855-3333-ACT.

An Introduction to the CeliAction Study

This is the first of a series of sponsored posts about the Celiaction Study on my page. Since being diagnosed with celiac disease in 2010 I have been patiently waiting for treatment options to augment the GF diet.  Although I eat strictly GF and am safely able to do so in my home, I am at risk of gluten cross-contamination whenever I travel and/or eat outside of my home.  The enzyme being studied has the potential to reduce intestinal damage from gluten cross-contamination, and is also being evaluated as a treatment for those with nonresponsive celiac disease.  All comments and questions will receive a response from a Celiaction Study representative. -Jess

celiactionblogpost

Managing celiac disease may be more than just a gluten-free diet.

A clinical research study called the CeliAction Study is researching if an investigational drug – which would be taken as a supplement to an attempted gluten-free diet – improves any symptoms of celiac disease.

You may qualify for the CeliAction Study if you:

  • Have been diagnosed with celiac disease by a healthcare professional
  • Are attempting to be on a gluten-free diet
  • Have experienced at least one moderate or severe symptom of celiac disease in the past month

If you participate in the CeliAction Study, you:

  • Will be able to maintain your current diet restrictions
  • Will be provided with study-related care at no cost
  • Do not need medical insurance to take part
  • May be compensated for time and travel
  • Will help advance medical research for celiac disease

To learn more about this research study and see if you qualify, visit CeliActionStudy.com
or call 1-855-3333-ACT.

Coeliac_path

Nonresponsive Celiac Disease

Nonresponders are the 5% of Celiac patients who have either persistent symptoms and/or abnormally high Celiac antibodies after two years on the gluten free diet.

According the most recent medical review in the “Up to Date” database, there are 5 main categories of nonresponders to the gluten free diet:

  1. Patient is continuing to eat gluten. This is the most common cause of persistent symptoms. This can be on purpose (i.e. taking a little bite of a gluten containing food every once in a while) or accidental (i.e. not realizing that a child is nibbling her wheat containing Playdough at school).
  2. Patient doesn’t actually have Celiac Disease.  For example, elevated serum antigliadin IgA antibodies may be a false positive. Small intestinal villous blunting may be caused by any of the following: hypogammaglobulinemia, acute infectious gastroenteritis, lymphoma, Crohn’s Disease, and/or a milk protein intolerance.
  3. There is a second disease present, in addition to Celiac, which is causing symptoms. Lactose intolerance, irritable bowel syndrome, small bowel bacterial overgrowth, pancreatic insufficiency, and microscopic colitis can all lead to digestive symptoms in patients with Celiac Disease. I recently wrote about having the dual diagnosis of Celiac Disease and Irritable Bowel Syndrome (see link).
  4. Refractory sprue is Celiac Disease which has never improved, or recurs after a period of “remission.”  It usually needs to be treated with steroids or other drugs that suppress the immune system, as it can lead to #5.
  5. Ulcerative jejunitis and/or intestinal lymphoma. Patients with ulcerative jejunitis have symptoms of malabsorption, fatigue, loss of appetite, weight loss, abdominal pain, diarrhea, and fever despite being on a gluten-free diet. Small bowel obstructions may occur.  Lymphomas have similar symptoms to ulcerative jejunitis, but may also be associated with fevers and abdominal masses.

The bottom line is that If you do not feel significantly better after two years on the gluten free diet, you need to work with your doctor to figure out the reason why. Untreated refractory sprue, ulcerative jejunitis, and lymphoma can lead to death. This is yet another reason to recommend screening to our family members…and if any of my 4 siblings are reading this, yes, you need to get tested or I will continue to badger you about this for this rest of your lives!

References:

1. Cleveland Clinic Center for Continuing Education.  “Celiac Disease and Malabsorptive Disorders.” By J. Wakim-Fleming.

2. “Management of Celiac Disease in Adults.” By Ciclitira, P.J.  UpToDate, April 10, 2013. www.uptodate.com.