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Secretory Immunoglobulin A, CD71, and Transglutaminase-2 Interactions Alter Permeability of Intestinal Epithelial Cells to Gliadin Peptides

Celiac.com 12/12/2012 - In duodenal biopsy samples from people with active celiac disease, the transferrin receptor, CD71, is up-regulated, and promotes retro-transport of secretory immunoglobulin A (SIgA)-gliadin complexes.

Photo: CC--Pat McDonaldTo better understand how interactions between SIgA and CD71 promote transepithelial transport of gliadin peptides, a team of researchers set out to determine if interactions among secretory immunoglobulin A, CD71, and transglutaminase-2 affect permeability of intestinal epithelial cells to gliadin peptides.

The research team included C. Lebreton, S. Ménard, J. Abed, I.C. Moura, R. Coppo, C. Dugave, R.C. Monteiro, A. Fricot, M.G. Traore, M. Griffin, C. Cellier, G. Malamut, N. Cerf-Bensussan, and M. Heyman. They are affiliated with the Mixed Research Unit 989 of the National Institute of Health and Medical Research (INSERM UMR989) in Paris, France.

For their study, the team evaluated duodenal biopsy specimens from 8 adults and 1 child with active celiac disease. The team used fluorescence-labeled small interfering RNAs against CD71 to transfect Caco-2 and HT29-19A epithelial cell lines.

They used flow cytometry, immunoprecipitation, and confocal microscopy to assess interactions among IgA, CD71, and transglutaminase 2 (Tgase2). They then assessed transcytosis of SIgA-CD71 complexes and intestinal permeability to the gliadin 3H-p31-49 peptide in polarized monolayers of Caco-2 cells.

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To assess physical interplay between SIgA and CD71 or CD71 and Tgase2 at the apical surface of enterocytes in biopsy samples and monolayers of Caco-2 cells, the team used fluorescence resonance energy transfer and in situ proximity ligation assays. They co-precipitated CD71 and Tgase2 with SIgA, bound to the surface of Caco-2 cells.

They found that SIgA-CD71 complexes were internalized and localized in early endosomes and recycling compartments, but not in lysosomes.

In the presence of celiac IgA or SIgA against p31-49, transport of intact 3H-p31-49 increased significantly across Caco-2 monolayers, while soluble CD71 or Tgase2 inhibitors interfered with transport.

Once it binds to apical CD71, SIgA (with or without gliadin peptides) enters a recycling pathway and avoids lysosomal degradation; this process allows apical-basal transcytosis of bound peptides. This mechanism is assisted by Tgase2 and might be involved in the pathogenesis of celiac disease.

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2 Responses:

 
Julie
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said this on
17 Dec 2012 10:02:03 AM PDT
Hi, I am trying to understand if this research pertains to me. I am IgA deficient and have been told by an allergist (not my gastro), that this might explain why I am very sensitive to gluten, because IgA helps to protect the intestines. Do you know if this is the case or if there is any research I could find about it? I've searched online but have come up with nothing about the particular subject of IgA deficiency and celiac patients.

 
Jenny
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said this on
19 Dec 2012 8:36:35 PM PDT
Not easily understood by the layperson. A 'translation' would be great!




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Hi! My daughter is 19 was diagnosed at age 16. It took about 12-18 month s for her to fully heal from the damage and feel "normal" again. Also because of the damage done she had reactions to dairy, so you may want to try no or minimum dairy until youre fully healed. Just a suggestion. Hope you start feeling well soon!

Hi yall! New to this blog, but really glad it exists because I have lots of questions. First off, I'm Allie! I'm 17 and newly diagnosed Celiac after about 3 years of searching for answers. I initially went gluten-free on the recommendation of a friend, I felt better in about a month and then my pediatric gastroenterologist had me do the gluten challenge, and my symptoms were the worst they have ever been, and ones I barely noticed before became very present. I did the biopsy and was diagnosed, it's been about 2 weeks and my symptoms are still pretty bad, although my diet has no known sources of gluten or cross contamination. Wondering if anyone has any input on healing post gluten challenge, any tips or how long it took for you would be quite helpful! Thanks

Might want to look into a keto diet, I have UC on top of celiacs and keto is working great Yeah I have major nerve and brain issues with gluten, gluten ataxia with nerve issues and brain issues. Seems to cause my body to attack my brain and nerve system. My brain stumbles fogs, and starts looping, the confusion causes me to become really irritable, I call it going Mr Hyde. Like my mind will start looping constantly on thoughts and not move driving me literally mad, or it used to. Now days it is primary the numbness anger but the gut issues and sometimes random motor loss limit me motionless to the floor now days for the duration of the major anger effects. Used to be a lot more mental then painful gut. I did a mental trauma post on it on while back where I came out about all my mental issues with gluten.

^^^^^^ good info, tips and tricks^^^^^^^^^ yes, crumbs will make you sick. also, breathing flour/pancake mix, etc that is in the air because eventually, you're going to swallow some.

Hello I was diagnosed Dec 15 of last year and went totally gluten-free the next day. I actually got worse before I got better - it's a steep learning curve - but now, 4 1/2 months later I'm finally seeing improvement. Hang in there.