There has been significant progress in the development of good blood tests for celiac disease. The same blood tests can be used to screen people at risk as well as help make the diagnosis. The tests are accurate enough that some experts believe small bowel biopsies may not be needed to diagnose CD in children.
The tests measure antibodies in the blood that are targeting specific substances called antigens. One antigen is tissue transglutaminase (tTG), which is present on intestinal cells, and is an “autoantigen” or normal part of the intestinal tract that stimulates antibodies in people with CD. Large amounts of immunoglobulin A (IgA) to tissue transglutaminase (IgA anti-tTG) almost always mean a person has celiac disease.
In the past, tests measured antibodies against gliadins, which are parts of gluten. However, antigliadin antibodies tests are not reliable enough to screen people or make the diagnosis of celiac disease. Researchers learned that people with CD make antibodies against modified gliadins, called deamidated gliadin peptides (DGP). Other blood tests now measure IgA antibody to DGP (IgA anti-DGP).
These are both good tests. There are different commercial kits used to measure the antibodies, and there can be slightly different results from different labs. Some doctors use both tests, some only one, to screen for celiac disease. Not only can these tests help make the diagnosis, but they can also be used to follow progress. IgA anti-tTG levels come down when people with CD follow a gluten-free diet.
However, there is one group of people who cannot be screened for CD with these tests. This is the group of people who have low levels of IgA, called IgA deficiency. Because they do not make a lot of IgA, they do not make enough IgA anti-tTG or IgA anti-DGP to test.
How big of a problem is this? By some estimates, one in 600 people of European descent is IgA deficient. It is also estimated that approximately 1% of this population has celiac disease. These two conditions are related. People with IgA deficiency are more likely to have asymptomatic celiac disease than people without the deficiency. Compared to people who have normal levels of IgA, they are 10 to 20 times more likely to have celiac disease. Research has also shown that IgA deficient individuals and people with celiac disease have similar HLA types, the underlying gene groups that predispose people to develop CD.
These two conditions are closely enough related that many experts recommended checking total IgA levels when doing celiac blood testing. If the results show IgA deficiency and neither of the celiac tests are positive, further evaluation must be done.
There are a number of different kinds of immunoglobulins, or antibodies. IgA is made in the intestine. IgG is made by blood cells that have been activated against an allergen or infectious agent. People who are IgA deficient usually still make IgG.
The only tests being used right now to diagnose celiac disease in people with IgA deficiency are IgG levels to the same antigens. IgG to tTG and IgG to DGP are the two levels that are measured.
A recently published study presented data about these tests from research done in Sweden. The researchers were able to look at information from 488,156 people screened for CD. Of these, there were 1,414 IgA deficient individuals, and of these, 356 agreed to participate in further study. 47 blood donors who were IgA negative served as control subjects; they had no symptoms of celiac disease. Not every study participant had all data collected, including lab tests and surveys, so the information is partially incomplete.
18.8% of the IgA deficient subjects (67) with suspected celiac disease had IgG anti-tTG antibodies, and from 15.7% (56) to 21.3% (76) had IgG anti-DGP, with one brand of test kit finding a higher number. 54 had celiac disease confirmed on intestinal biopsy.
There were also some individuals from the blood donation group who had positive IgG tests, and four went on to have biopsy-proven celiac disease. There were 58 total patients in the study with definite CD. 63% (34) were IgG anti-tTG positive. 52% (28) were positive for IgG anti-DGP with one test kit and 65% (35) with the other test kit. There was no one test guaranteed to give a positive result in patients who actually did have celiac disease and IgA deficiency.
One other type of blood test can be done, which is HLA typing, looking for the genes that make a person susceptible to CD. If someone does not have either types HLA-DQ2 or DQ8, they almost certainly do not have celiac disease. Someone with one of these genes, IgA deficiency and negative IgG tests with symptoms or signs of celiac disease may still need small bowel biopsies.
This study confirms that at the current time, blood tests for the diagnosis of celiac disease in people with IgA deficiency are not as accurate as those for people who have normal IgA. In addition, the researchers looked at the IgG levels when people with CD were on a gluten-free diet. They were just as high in some of the individuals on the gluten-free diet as those not on the diet. The researchers noted that this has been seen in other studies. While IgA antibody levels are useful in following people with celiac disease and correlate with their dietary adherence, the same cannot be said of IgG antibodies.
Physicians should order these IgG tests on patients with suspected CD who have IgA deficiency.
It is very likely that better blood tests will be developed in the future, but at this time, all the available information must be considered carefully in IgA deficient individuals with possible celiac disease.
Ning Wang, Lennart Truedsson, Kerstin Elvin, et al. Serological Assessment for Celiac Disease in IgA Deficient Adults. PLOS ONE. www.plosone.org 1 April 2014 | Volume 9 | Issue 4 | e93180