Blood Test/diagnosis Question

[basilicious]

I apologize if this is something I should have already figured out in my research, but my annoyance with the diagnostic process is clouding my thinking at the moment...

If the DGP IgG test is so accurate and so specific to celiac (which I realize it is), then why would we need any other blood tests? Why are people still getting full celiac panels for the wide array of antibodies? Why are biopsies still being used to confirm diagnosis? Are there ever false positives or other underlying reasons for the DGP IgG test?

What constitutes sufficient "proof" of celiac? Although it's clearly useful to try to size up damage and rule out other conditions, can't that be a next step after a celiac diagnosis? I am genuinely trying to understand if I'm missing something or if it truly just boils down to the medical field only diagnosing advanced celiac!

I keep seeing how DGP IgG is so great at diagnosing celiac when someone is low in total IgA or is very young, but I don't understand why it would be limited to that group. If it's good, it's good, and shouldn't everyone use it?

Sorry for so many questions...thanks for humoring me.

[Skylark]

Scientists are comparing them even as we type. It looks like the combo of DGP-IgG and TTG-IgA may be the best bet to help reduce false positives.

Open Original Shared Link

Open Original Shared Link

[basilicious]

Scientists are comparing them even as we type. It looks like the combo of DGP-IgG and TTG-IgA may be the best bet to help reduce false positives.

Open Original Shared Link

Open Original Shared Link

Skylark, as usual, you are able to school me! I will have to find the full text of these online.

Not trying to be thick-headed here, but since this points to a combo of DGP-IgG and TTG IgA, then what about the folks (like me) who are positive for DGP IgG but not TTG IgA? Isn't the chance of a false positive extremely slim? Are you aware of anything else besides celiac that could cause a high DGP IgG? (For example, my GI doctor said it could be related to a wheat allergy, which seems far-fetched, but what do I know...)

Related to this...is it true that testing DGP IgG could detect celiac earlier than some of the other antibodies tests? So should I feel confident in my results and feel fortunate to have possibly caught this at an earlier stage?

[Skylark]

From what I've been reading DGP IgG is thought to be the first celiac antibody formed. Then when antibodies bind to the gliadin-TTG enzyme complex you end up with TTG antibodies and autoimmunity. Your doctor may be thinking of DGP-IgA, which is not as sensitive for celiac. The putative development of DGP-IgG before TTG does raise the question of how far into celiac disease you get DGP, assuming that is the correct sequence of events. I agree with you that false positives seem unlikey and that you were probably lucky and caught early in the process of developing celiac.

It looks like the DGP-IgG is actually slightly less sensitive in one of these two studies than TTG-IgA. The combination is preferred because of the high specificity.

Let's see. In the Vermeersch et al. paper they were working with a bunch of different DGP IgG tests. The best had 86% sensitivity and 98% specificity. Their other kits ranged in sensitivity from 40.7%-86% at a 98% sensitivity cutoff.

"When the IgG anti-DGP assay from Inova would be performed in all patients in addition to the IgA anti-tTG assay from Phadia (the IgA anti-tTG and IgG anti-DGP assay with the highest LR in this study), the sensitivity would increase from 83.7% to 89.5%, while the specificity would only decrease from 98.4% to 98.0%. Five of the 14 patients diagnosed with celiac disease who were negative for IgA anti-tTG were positive for IgG anti-DGP including one patient with a selective IgA deficiency (< 0.05 g/L). Sixty-seven of the 86 celiac disease patients were positive with both assays compared to only 2 of the 741 patients classified as non-celiac disease. These 2 patients who were Marsh 0 on intestinal biopsy could have latent celiac disease. One 5 year old patient had a small stature and another 4 year old patient had abdominal pain."

From Volta et al.

"In the light of the information provided by our prospective study, as hypothesized by other authors,23 a new antibody strategy based on the combined search for IgA tTGA and IgG DGP-AGA can be designed for celiac disease screening. As generally recognized, IgA tTGA are the most sensitive test for celiac disease, but their usefulness can be partially reduced by the occurrence of “false positives,” a lower sensitivity in infancy and the inability to identify celiac disease cases associated with IgA deficiency. Indeed, IgG DGP-AGA may be suggested to solve these diagnostic deficiencies of IgA tTGA and add significant advantages for the serologic workup of celiac disease. Specifically: (1) IgG DGP-AGA can replace IgA EmA as a confirmatory test for tTGA positive cases. Indeed, although both IgG DGP-AGA and EmA are highly specific for celiac disease, the former (as it uses ELISA) offers the advantage of better reproducibility than the latter, whose reliability is limited by interobserver variability owing to the interpretation of the indirect immunofluorescence pattern 24; (2) IgG DGP-AGA are a very good tool for identifying celiac disease in children under 2 years of age, rendering testing for AGA redundant in these patients,25, Volta unpublished data finally, and (3) IgG DGP-AGA allows the identification of celiac disease in patients with IgA deficiency, thus avoiding the IgG tTGA test. In this respect, IgG DGP-AGA should undoubtedly be preferred to IgG tTGA, which is known to have a very low specificity for celiac disease.4 Taken together, the results that emerge from this study lead us to propose just the 2 IgA tTGA and IgG DGP-AGA tests instead of 4 assays (that is IgA tTGA, IgA EmA, IgA AGA, and IgG tTGA) for celiac disease screening. If confirmed by other studies, this strategy will mean both a significant saving of resources and an improvement in diagnostic accuracy for celiac disease."

[basilicious]

Thank you for taking the time to share these excerpts, Skylark! My alumni access to online research can be a bit testy.

This makes a lot more sense. While I've been focused on the false positive angle, I realize the more important issue from a broader testing perspective is how sensitive IgG DGP is and whether it will detect celiac at various stages. Alone, IgG DGP satisfies the former but possibly not the latter.

This sounds like a major advance in that, between IgG DGP and TTG-IgA, there is not only strong sensitivity but also the ability to detect celiac over time, including early on. Let's hope they soon develop a diagnostic timeline that fully maps out the testing required to effectively detect celiac at all stages...but maybe they're already there with this combo.