Fewer IgA Anti-transglutaminase Autoantibodies at Type 1 Diabetes Onset Linked with Lower Celiac-Specific Immune Response

Celiac.com 04/11/2022 - Researchers and clinicians are just beginning to understand the many connections between celiac disease and diabetes. We've done a number of articles on links between celiac disease and diabetes.

We've talked about how a gluten-free diet might help lower diabetes risk. We've looked at the potential role of gluten in Type 1 Diabetes.

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We've even asked if having type 1 diabetes mellitus and celiac disease automatically mean worse health and quality of life?

We know that rates of diabetes are much higher in celiacs than in the general population, and vice versa. We also know that non-diabetic patients often show celiac-specific humoral immunoreactivity at the time of their celiac disease diagnosis. What about diabetic patients? Do they show type 1 diabetes celiac-specific humoral immunoreactivity?

To find out, a research team recently looked at celiac-associated humoral autoimmunity in child, adolescent, and adult patients at the onset of type 1 diabetes (DM1) to see if those patients exhibit DM1 celiac-specific humoral immunoreactivity, as do non-diabetic celiac patients at first diagnosis.

The research team included Claudio Tiberti Aceliac disease, Francesca Panimolle BS, Margherita Bonamico MD, Blegina Shashaj MD, Tiziana Filardi MD, Federica Lucantoni BS, Raffaella Nenna MD, Francesco Costantino MD, Andrea Lenzi MD, and Susanna Morano MD. They are variously affiliated with the Department of Internal Medicine, University of Rome “Sapienza,” Rome, Italy; the Department of Pediatrics, University of Rome “Sapienza,” Rome, Italy; and the Department of Physiopathology, University of Rome “Sapienza,” Rome, Italy.

The team found IgA anti-transglutaminase autoantibodies (IgA-tTGAb) in more than 650 new-onset DM1 serum samples.  They then analyzed IgA-tTGAb-positive DM1 samples for IgG-tTG, deamidated gliadin (DGP), and actin antibodies, and compared the results against those from more than 80 screen-detected non-diabetic patients at the time of their celiac diagnosis.

In all, nearly thirteen percent of DM1 samples were positive for IgA-tTGAb, with patients 18 years or over showing lower autoantibody frequency, that's about 2.2 times more than in adult patients.

Meanwhile, compared with non-diabetic celiacs, IgA-tTGAb+ DM1 patients showed substantially lower IgA-tTGAb titers, IgG-tTGAb, and DGPAb frequency/titers, along with sharply lower average number of celiac-autoantibody positive results per patient. 

These results show that the age of diabetes onset is negatively associated with risk of celiac disease, that is, the lower age of DM1 onset, the higher the risk of developing celiac disease. Compared with the activity of non-diabetic patients at the time of celiac diagnosis, celiac-specific humoral immunoreactivity is sharply lower at the onset of DM1.

The team suggests that a general lower celiac-specific humoral immune response reflects a slower process of celiac disease development in DM1 patients, which is marked by nearly imperceptible gastrointestinal symptoms. 

This hypothesis is supported by an autoimmune diabetes study that shows a direct correlation between intensity of the humoral immune response and more prominent characteristics of insulin deficiency.*

Stay tuned for more stories on connections between celiac disease and diabetes.

Read more in Diabetes Care. 2012 Oct; 35(10): 2083–2085
 

*Buzzetti R, Di Pietro S, Giaccari A, et al. Non Insulin Requiring Autoimmune Diabetes Study Group High titer of autoantibodies to GAD identifies a specific phenotype of adult-onset autoimmune diabetes. Diabetes Care 2007;30:932–938