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What's the Connection Between Seronegative Celiac Disease and Immunoglobulin Deficiency?

Celiac.com 11/04/2015 - A research team that conducted an analysis of the relationship between seronegative celiac disease and immunoglobulin deficiencies also conducted a literature search on the main medical databases, which revealed that seronegative celiac disease poses a diagnostic dilemma.

Image: CC--Valerie EverettThe research team included F. Giorgio, M. Principi, G. Losurdo, D. Piscitelli, A. Iannone, M. Barone, A. Amoruso, E. Ierardi, and A. Di Leo. They are variously affiliated with the Section of Gastroenterology at University Hospital Policlinico, Department of Emergency and Organ Transplantation at University of Bari in Bari, Italy.

They note that villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers in addressing seronegative celiac disease. They also note that immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of seronegative celiac disease patients may be useful.

In the team's view, tTG-mRNA was similarly increased in seropositive celiac disease and suspected seronegative celiac disease, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders.

An immune deregulation, severely lacking B-cell differentiatio, underlies the association of seronegative celiac disease with immunoglobulin deficiencies. Therefore, celiac disease may be linked to autoimmune disorders and immune deficits, known as common variable immunodeficiency (CVID)/IgA selective deficiency.

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CVID is a heterogeneous group of antibody dysfunction, whose association with celiac disease revealed only by a positive response to a gluten-free diet. The research team suggests a possible familial inheritance between celiac disease and CVID.

Selective IgA deficiency, commonly associated with celiac disease, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare, with less than 300 documented cases, and is connected to celiac disease in 5% of cases.

The team diagnosed seronegative celiac disease in a patient affected by sIgMD using the tTG-mRNA assay. One-year on a gluten-free diet restored IgM levels.

This study data support a link between seronegative celiac disease and immunoglobulin deficiencies, and invites researchers to take a closer look at this connection.

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It took me 20 years or more Barry so I wouldn't claim any great insight on this I had a 'eureka' moment, up until then I was walking around with multiple symptoms and not connecting any dots whatsoever. It is very, very difficult to diagnose and that's something that's reflected in so many of the experiences detailed here. A food diary may help in your case. It helped me to connect the gaps between eating and onset. It could help you to track any gluten sources should you go gluten free. It is possible for your reactions to change over time. As to whether its celiac, that's something you could explore with your doctor, stay on gluten if you choose to go that way. best of luck! Matt

I took Zoloft once. Loved it until it triggered microscopic colitis (colonoscopy diagnosed it). Lexapro did the same. However, I have a family member who is fiagnosed celiac and tolerates Celexa well.

Thanks for the update and welcome to the club you never wanted to join! ?

Jmg, I am glad you were able to come to the realisation that the culprit was in fact gluten. For me its not so simple. IBS runs in the family, as do several food intolerances. Its just in the last while that I can finally reach the conclusion that for me its gluten. The fact that it is a delayed effect-several hours after, made it harder. Friday I had some KFC, felt great. Saturday evening felt sleepy, Sunday felt awful and my belly was huge. I think I have gone from mildly sensitive to full blown celiac over the course of five years-if that possible. Thanks for all your help.

I thought I'd take a moment to provide an update, given how much lurking I've done on these forums the last year. It took a long time, but I've since had another gastroenterologist visit, many months of eating tons of bread, and an endoscopy where they took several biopsies. I have to say, the endoscopy was a super quick and efficient experience. During the procedure they let me know that it looked somewhat suspicious, causing them to take many biopsies, and then did comprehensive blood work. About a month later, I received a call telling me that the TTG came back positive a second time, and that the biopsies were a mix of negative (normal) results and some that were positive (showing blunting of the villi). As a result, I've been given a celiac diagnosis. It's been about a month now that I've been eating gluten free. Not sure if I'm really feeling all that different yet. It's a bit twisted to say, but in some way I was hoping for this diagnosis ? thinking how nice it would be to have an explanation, a plan of action, and feeling better. It's certainly no small change to be totally gluten free, but I'm hopeful.