No popular authors found.
Ads by Google:

Categories

No categories found.


Get Celiac.com's E-Newsletter




Ads by Google:



Follow / Share


  FOLLOW US:
Twitter Facebook Google Plus Pinterest RSS Podcast Email  Get Email Alerts

SHARE:

Popular Articles

No popular articles found.
Celiac.com Sponsors:

IL-15 Triggered Pathway in Intraepithelial Lymphocytes Emerges as New Factor in Type II Refractory Celiac Disease and Enteropathy-associated T Cell Lymphoma


Celiac.com 05/19/2010 - Enteropathy-associated T cell lymphoma is a serious complication of celiac disease, and a major cause of mortality in untreated celiac disease.

One possible trigger for Enteropathy-associated T cell lymphoma development is chronic exposure of intraepithelial lymphocytes (IELs) to strong anti-apoptotic signals, that is, signals that interfere in the normal mortality of the IEL cells. These signals are triggered by IL-15, a cytokine that is over-expressed in the enterocytes of people with celiac disease.

However, researchers have not yet fully mapped the signaling pathway by which IL-15 transmits these anti-apoptotic signals. Researchers consider type II refractory celiac disease (RCDII) to be a middle step between celiac disease and enteropathy-associated T cell lymphoma.

Eliminating abnormal IELs at the RCDII stage would likely block EATL development. So far, though, scientists have not found successful immunosuppressive and/or chemotherapeutic approaches able to accomplish this, and RCDII outcomes remain very poor.

A team of researchers recently set out to map the IL-15–driven survival pathway in human IELs, and to determine whether IL-15 triggered pathway in human intraepithelial lymphocytes represents a possible new target in type II refractory celiac disease and enteropathy-associated T cell lymphoma.

The research team was made up of Georgia Malamut, Raja El Machhour, Nicolas Montcuquet, Séverine Martin-Lannerée, Isabelle Dusanter-Fourt, Virginie Verkarre, Jean-Jacques Mention, Gabriel Rahmi, Hiroshi Kiyono, Eric A. Butz, Nicole Brousse, Christophe Cellier, Nadine Cerf-Bensussan, and Bertrand Meresse.

Ads by Google:

The are variously affiliated with INSERM U989, the Université Paris Descartes, Faculté de Médecine René Descartes, the Department of Gastroenterology, AP-HP, Hôpital Européen Georges Pompidou, the Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), INSERM U1016, the Department of Pathology, AP-HP, of the Hôpital Necker-Enfants Malades in Paris, with the Division of Mucosal Immunology, Department of Microbiology and Immunology at the Institute of Medical Science at the University of Tokyo in Japan, and the Inflammation Department of AMGEN Inc., in Seattle, Washington, USA.

Their current findings reveal that the survival signals IL-15 directs to freshly isolated human IELs, and to human IEL cell lines derived from celiac disease patients with type II refractory celiac disease, depend on anti-apoptotic factors Bcl-2 and/or Bcl-xL.

The signals require IL-15Rβ, Jak3, and STAT5 for proper function, but functioned independently of PI3K, ERK, and STAT3. In support of these findings, the team recorded elevated levels of Bcl-xL, phospho-Jak3, and phospho-STAT5 in IELs from patients with active celiac disease and RCDII.

Moreover, by incubating patient duodenal biopsies with a fully humanized human IL-15–specific Ab, the team effectively blocked Jak3 and STAT5 phosphorylation.

Also, treatment with IL-15–specific Ab caused IEL cell mortality, and wiped out the massive IEL build-up in mice over-expressing human IL-15 in their gut epithelium.

The study marks the first successful mapping of the IL-15–driven survival pathway in human IELs, and demonstrates that IL-15 and its downstream effectors are meaningful therapeutic targets in RCDII.

These findings will likely help to pave the way for the development of successful immunosuppressive and/or chemotherapeutic treatments that destroy abnormal IELs at the RCDII stage and help to block EATL development, improving outcomes for RCDII patients.

Source:

Celiac.com welcomes your comments below (registration is NOT required).





Spread The Word







Related Articles



Comments




Rate this article and leave a comment:
Rating: * Poor Excellent
Your Name *: Email (private) *:




In Celiac.com's Forum Now:

All Activity
Celiac.com Celiac Disease & Gluten-Free Diet Forum - All Activity

you're lucky you dont catch colds. im the opposite i catch everything very easily and get alot sicker than whoever i caught it from and take much longer to get better.

Even one positive can be diagnostic. This is one: Gliadin deamidated peptide IgG 33.9. If unsure, a biopsy of the small intestine will provide definite confirmation. There is a control test to validate the other ones, but I don't see it there. What is does is validate the others by checking on the overall antibody levels. But it is to detect possible false negatives. A positive is a positive. I think your daughter has joined our club.

My daughter, almost 7 years old, recently had a lot of blood work done, her Dr is out of the office, but another Dr in the practice said everything looked normal. I'm waiting for her Dr to come back and see what she thinks. I'm concerned because there is one abnormal result and I can't find info to tell me if just that one test being abnormal means anything. The reason for the blood work is mainly because of her poor growth, though she does have some other symptoms. IgA 133 mg/dl Reference range 33-200 CRP <2.9 same as reference range Gliadin Deamidated Peptide IgA .4 Reference range <=14.9 Gliadin deamidated peptide IgG 33.9 Reference range <=14.9 TTG IgA .5 Reference range <=14.9 TTG IgG <.8 Reference range <=14.9

Just watch out. I just went to the expo in Schaumburg, IL, and ended up getting glutened. I realized afterward that I ate all these samples thinking they were gluten free, and they weren't. One company was advertising some sugar, and had made some cake, but then I realized.... How do I know if this contains any other ingredients that might have gluten? Did they make it with a blender or utensils that had gluten contamination? Makes me realize the only safe things would be packaged giveaways with gluten free labeling. My fault for not thinking things through. It was just too exciting thinking i could try it all and enjoy without worry.

No fasting required for a celiac blood test unless they were checking your blood glucose levels during the same blood draw.