IgA is the abbreviation for immunoglobulin A and refers to a group of antibodies that perform a specific task as part of our immune system. They are primarily found on mucous membranes, such as in the gastrointestinal tract and respiratory tract. In this article, I would like to explain what they have to do with celiac disease and how a deficiency affects the body. Below, you can also download a checklist and the detailed procedure for diagnosing an IgA deficiency.

What are antibodies and which ones exist?

In another post, I have already explained the basic structure of our immune system and the role antibodies play in it. To repeat it briefly here: Antibodies are specifically produced by certain white blood cells (B lymphocytes) to target foreign substances such as viruses. This allows our immune system to combat these pathogens in a very targeted manner. Since the antibody must first be "manufactured"—a kind of tailor-made solution—it takes a little longer until it is available. However, our immune system remembers the contact, so that upon the second encounter with the same virus, the antibody can be reactivated very quickly.

Our immune system can produce different antibody groups, as I explain in more detail in the previous post. But here is a very brief summary again: there are antibodies of groups A, E, G, and M. They are also known as immunoglobulins, which leads to the abbreviations IgA, IgE, IgG, and IgM. In this post, I would like to focus on IgA:

What is an IgA deficiency?

With an incidence of approximately one in 500-700 people, IgA deficiency is the most common immunodeficiency in our population. In most cases, this involves a so-called selective IgA deficiency, meaning that only IgA production is impaired. Combined immunodeficiencies also occur, which involve other antibody groups or other components of the immune system.

• In an absolute deficiency, the body cannot produce any IgA antibodies. The measured blood value is then below 7 mg/dl – for comparison: the normal range for adults begins at 70 mg/dl.

• If values between 7 and 70 mg/dl are measured, this is referred to as a relative deficiency. These individuals can produce IgA, but significantly less than usual.

Since IgA production is generally quite low in the first few years of life, these threshold values for a deficiency only apply after the fourth birthday.

How does an IgA deficiency manifest itself?

You probably think that an immunodeficiency should be immediately apparent, especially when the first line of defense against pathogens on the mucous membranes is missing. This is certainly true – about half of the people with an IgA deficiency show an increased susceptibility to infection, particularly to bacterial infections such as otitis media and upper respiratory tract infections. In fact, they also more frequently develop chronic inflammatory bowel diseases and autoimmune diseases such as celiac disease, as well as others affecting the thyroid or those within the rheumatological spectrum. About one third of the individuals who are symptomatic with IgA deficiency have an additional autoimmune disease. Allergies are also observed more frequently, occurring in the respiratory tract in the form of hay fever or asthma, on the skin as allergic eczema, or in the gastrointestinal tract as a food allergy.

However, the other half of those affected have no symptoms of this immune deficiency. This is because our immune system is so complex that its various components can complement and compensate for one another. As a result, an IgA deficiency often remains undiagnosed – until the blood levels are tested for IgA antibodies and it is discovered that they are too low.

What does IgA deficiency have to do with celiac disease?

As I wrote above, celiac disease occurs more frequently in people with an IgA deficiency. Depending on the study, the prevalence is between 2 and 8%, compared to about one percent in the general population. The lack of this primary antibody barrier allows for a more altered immune response to food components and can therefore contribute to the development of this autoimmune disease. Furthermore, the immune system seems more prone to an autoimmune reaction due to the defect.

While celiac disease is more common with IgA deficiency, this significantly complicates the diagnosis of celiac disease in these patients:

IgA antibodies, such as the tissue transglutaminase IgA antibody (abbr.: tTG-IgA-Ab), are predominantly used in the diagnosis of celiac disease. However, if a person cannot form IgA antibodies because they have an absolute IgA deficiency, they will not produce IgA-type celiac antibodies either. A negative antibody test is interpreted by many doctors and other individuals as meaning there is no suspicion of celiac disease. Since IgA deficiency is often undiagnosed, one would not notice that the patient is unable to produce celiac-specific IgA antibodies. Therefore, a total IgA level must always be tested, at least the first time. Only then can a negative celiac IgA antibody result be interpreted correctly:

• tTG-IgA-Ab and total IgA within normal range -> celiac disease unlikely
• tTG-IgA-Ab elevated -> suspicion of celiac disease -> further clarification. You can find the procedure here
• tTG-IgA-Ab within normal range, but total IgA reduced -> further examinations

Diagnostic approach in cases of confirmed IgA deficiency

If there is a suspected case of celiac disease and the tTG-IgA antibody values are unremarkable, but an IgA deficiency has been confirmed at the same time, further examinations are necessary: In addition to celiac disease IgA antibodies, corresponding IgG antibodies can also be tested. These are used in the event of an IgA deficiency – and only then. Otherwise, IgG antibodies provide no additional benefit and only result in increased costs.

You can test for both IgG antibodies against tissue transglutaminase and against deamidated gliadin peptides (abbrev.: DGP). Both tests can be performed as an alternative; it is not necessary to perform both.

If the IgG antibody against tTG or DGP is abnormal, a gastroscopy with a small intestinal biopsy must be performed next to confirm celiac disease. In this case, there is no way to reliably diagnose celiac disease in either children or adults without this procedure. The diagnosis of celiac disease is then established from these two examinations, with elevated tTG or DGP IgG antibodies and clearly altered mucosa in the duodenum.

Individuals with a relative IgA deficiency are able to produce a certain level of IgA antibodies. If elevated tTG-IgA antibodies can be detected in them, the standard procedure can also be used even if total IgA is (slightly) below the age-appropriate norm. If total IgA is below the norm, even if only slightly, and the tTG-IgA antibody is not conclusive, then the IgG antibody against tTG or DGP must always be tested subsequently.