The effects of modified versus unmodified wheat gluten administration in patients with celiac disease.
Celiac disease (CD) treatment requires a gluten-free diet (GFD), although alternative approaches have been proposed. Modification of gliadin peptides using microbial transglutaminase (mTG) inhibits their ability to induce immune response in vitro. Our aim was to evaluate the safety of mTG-modified wheat flour ingestion in CD patients. Twenty-one CD patients in remission were randomized to receive mTG-modified (n=11) or unmodified (n=10) wheat flour rusks, in double-blind fashion. Monthly, patients completed a symptom questionnaire. Serum anti-tTG, EMA and creatinine levels were monitored. At baseline and after 90days, serum anti-actin antibodies (AAA) were measured and upper endoscopy was performed. Data were analyzed by non-parametric tests. 7/11 patients eating modified rusks and 7/10 patients receiving unmodified rusks completed the study. At baseline, all patients showed negative serum anti-tTG and EMA results. At the end, 2/7 (28.6%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented positive serum anti-tTG and EMA results. Creatinine results were unmodified. Moreover, 1/7 (14.3%) patients ingesting modified and 4/7 (57.1%) patients taking unmodified rusks presented villous atrophy. In patients who received unmodified rusks, the AAA levels increased significantly and duodenal anti-tTG levels appeared higher than those measured in patients who ate modified rusks. Abdominal swelling, bloating and nausea were more severe in patients ingesting unmodified rusks than those taking modified rusks. Our results may support larger clinical trials to confirm the enzymatic treatment of wheat flour as an alternative to GFD. Clinicaltrials.gov registration no: NCT02472119.
Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy.
Mariacatia
M
Marino
Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy.
Rossella
R
Casale
Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy.
Raffaele
R
Borghini
Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy.
Sara
S
Di Nardi
Department of Clinical Medicine, Sapienza University, Rome, Italy.
Giuseppe
G
Donato
UOC DLC07 Laboratory Analysis DEA, Policlinico Umberto I, Rome, Italy; Department of Molecular Medicine, Sapienza University, Rome, Italy.
Antonio
A
Angeloni
IPAFOOD srl, Frigento, AV, Italy.
Salvatore
S
Moscaritolo
IPAFOOD srl, Frigento, AV, Italy.
Lorenza
L
Grasso
Institute of Food Sciences, National Research Council, Avellino, Italy.
Giuseppe
G
Mazzarella
Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy.
Marco
M
Di Tola
Institute of Food Sciences, National Research Council, Avellino, Italy.
Mauro
M
Rossi
Department of Internal Medicine and Medical Specialties, Sapienza University, Rome, Italy. Electronic address: antonio.picarelli@uniroma1.it.
Antonio
A
Picarelli
D000199:Actins / Q000276:immunology; D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D002446:Celiac Disease / Q000276:immunology* / Q000628:therapy; D002478:Cells, Cultured; D004035:Diet Therapy; D055050:Diet, Gluten-Free; D005260:Female; D005903:Gliadin / Q000276:immunology / Q000378:metabolism*; D005983:Glutens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D056724:Immunity, Humoral; D007558:Italy; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011503:Transglutaminases / Q000276:immunology / Q000378:metabolism*; D014908:Triticum / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
D000199:Actins; D000907:Antibodies, Bacterial; D001323:Autoantibodies; D001426:Bacterial Proteins; D010446:Peptide Fragments; D005983:Glutens; D005903:Gliadin; D011503:Transglutaminases
Alternative celiac disease treatment; Celiac disease; Enzyme-modified wheat flour; Gluten-free diet; Microbial transglutaminase