Researchers Look at Role of TG6 Auto-Antibodies in Dermatitis Herpetiformis

Celiac.com 04/28/2021 - Dermatitis herpetiformis is an external skin manifestation of gluten sensitivity. In people with dermatitis herpetiformis, an autoimmune response targets transglutaminase 3 (TG3) in the skin. Transglutaminase 2 (TG2) is a celiac disease autoantigen marked by the presence of enteropathy, while TG6 is the autoantigen that plays a role in neurological manifestations of gluten sensitivity. 

Researchers don't fully understand the interplay between B cell responses to these three transglutaminases in developing the clinical spectrum of disease manifestations. They also do not fully understand the individual or combined diagnostic and predictive value of the respective autoantibodies. 

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To get a better idea of those values, a team of researchers recently assessed rates of TG6 antibodies in a group of patients with dermatitis herpetiformis.

The research team included Marios Hadjivassiliou, Timo Reunala, Kaisa Hervonen, Pascale Aeschlimann, and Daniel Aeschlimann. They are variously affiliated with the Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust and University of Sheffield in Sheffield, UK; the Department of Dermatology, Tampere University Hospital in Tampere, Finland; the Celiac Disease Research Center, Tampere University and Faculty of Medicine and Health Technology in Tampere, Finland; and the Matrix Biology and Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University in Cardiff, UK.

The team looked at rates of TG6 antibodies in a group of 33 patients with dermatitis herpetiformis. Thirteen of the 33 patients (39%) were positive for TG6, 11 for IgA, three for IgG, and one for both. This was substantially higher than the 14% rate seen classic celiac disease cases in a Finnish population. 

Sixty percent of dermatitis herpetiformis patients with no enteropathy, ten patients in all, were TG6 positive, compared with 17% percent of those showing overt enteropathy, twelve in all (Marsh IIIB). 

Gluten-Free Diet Improves TG6 Antibody Levels

After one year on a gluten-free diet, repeat testing showed that seven patients were TG6 negative, while 85% (11 of 13) showed reduced titers for TG6 antibodies. Four patients seroconverted and tested positive for TG6 antibodies at one year, due to the ongoing exposure to gluten. 

The team reports another patient who presented with encephalopathy leading to the diagnosis of celiac disease, who was intermittently adhering to a gluten-free diet. 

At baseline serological testing, the patient was positive for antibodies to all 3 transglutaminases. Eleven years later, he developed dermatitis herpetiformis, and eventually developed ataxia and peripheral neuropathy. 

Even though TG3 and TG6 autoantibodies are associated to certain disease expressions, TG2, TG3, and TG6 autoantibodies can be present across the spectrum of GRD patients, and may develop years before extra-intestinal symptoms appear. 

This supports the idea that gluten-dependent adaptive immunity is a necessary, but not sufficient condition for the development of organ-specific damage. 

TG6 antibodies seem to develop more frequently in patients with gluten intolerance, but, either there was no development of the molecular state driving the tissue damage in the gut, or more likely perhaps, a greater resistance to developing the phenotype in the first place.

Read the full report in Nutrients 2020, 12(9), 2884