Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease.

Autor:	Croese J; The Department of Gastroenterology and Hepatology, The Prince Charles Hospital, Brisbane, Australia.; Center for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia., Miller GC; Envoi Specialist Pathologists, Brisbane, Australia., Marquart L; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Llewellyn S; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Gupta R; Center for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia., Becker L; Center for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia., Clouston AD; Envoi Specialist Pathologists, Brisbane, Australia., Welch C; Department of Gastroenterology, Townsville University Hospital, Townsville, Australia., Sidorenko J; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia., Wallace L; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia., Visscher PM; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia., Remedios ML; Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Australia., McCarthy JS; QIMR Berghofer Medical Research Institute, Brisbane, Australia., O'Rourke P; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Radford-Smith G; QIMR Berghofer Medical Research Institute, Brisbane, Australia., Loukas A; Center for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia., Norrie M; Gastroenterology and Hepatology, Logan Hospital, Brisbane, Australia., Masson JW; Department of Gastroenterology, Townsville University Hospital, Townsville, Australia., Gearry RB; Department of Medicine, University of Otago, Christchurch and Canterbury District Health Board, Christchurch, New Zealand., Rahman T; The Department of Gastroenterology and Hepatology, The Prince Charles Hospital, Brisbane, Australia.; Center for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia., Giacomin PR; Center for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Jazyk:	angličtina
Zdroj:	Clinical and translational gastroenterology [Clin Transl Gastroenterol] 2020 Dec; Vol. 11 (12), pp. e00274.
DOI:	10.14309/ctg.0000000000000274
Abstrakt:	Introduction: Celiac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled. Methods: We undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease. The 94-week study involved treatment with either 20 or 40 Necator americanus third-stage larvae (L3-20 or L3-40) or placebo, followed by escalating gluten consumption (50 mg/d for 12 weeks, 1 g intermittent twice weekly for 12 weeks, 2 g/d sustained for 6 weeks, liberal diet for 1 year). Results: Successful study completion rates at week 42 (primary outcome) were similar in each group (placebo: 57%, L3-20: 37%, and L3-40: 44%; P = 0.61), however gluten-related adverse events were significantly reduced in hookworm-treated participants: Median (range) adverse events/participant were as follows: placebo, 4 (1-9); L3-20, 1 (0-9); and L3-40, 0 (0-3) (P = 0.019). Duodenal villous height:crypt depth deteriorated similarly compared with their enrolment values in each group (mean change [95% confidence interval]: placebo, -0.6 [-1.3 to 0.2]; L3-20, -0.5 [-0.8 to 0.2]; and L3-40, -1.1 [-1.8 to 0.4]; P = 0.12). A retrospective analysis revealed that 9 of the 40 L3-treated participants failed to establish hookworm infections. Although week 42 completion rates were similar in hookworm-positive vs hookworm-negative participants (48% vs 44%, P = 0.43), quality of life symptom scores were lower in hookworm-positive participants after intermittent gluten challenge (mean [95% confidence interval]: 38.9 [33.9-44] vs 45.9 [39.2-52.6]). Discussion: Hookworm infection does not restore tolerance to sustained moderate consumption of gluten (2 g/d) but was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses.
Databáze:	MEDLINE
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