Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease

Croese, John, Giacomin, Paul, Navarro, Severine, Clouston, Andrew, McCann, Leisa, Dougall, Annette, Ferreira, Ivana, Susianto, Atik, O'Rourke, Peter, Howlett, Mariko, McCarthy, James, Engwerda, Christian, Jones, Dianne and Loukas, Alex (2015) Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. Journal of Allergy and Clinical Immunology, 135 2: 508-516.e5. doi:10.1016/j.jaci.2014.07.022

Author Croese, John
Giacomin, Paul
Navarro, Severine
Clouston, Andrew
McCann, Leisa
Dougall, Annette
Ferreira, Ivana
Susianto, Atik
O'Rourke, Peter
Howlett, Mariko
McCarthy, James
Engwerda, Christian
Jones, Dianne
Loukas, Alex
Title Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease
Journal name Journal of Allergy and Clinical Immunology   Check publisher's open access policy
ISSN 1097-6825
Publication date 2015-02-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.jaci.2014.07.022
Open Access Status Not Open Access
Volume 135
Issue 2
Start page 508
End page 516.e5
Total pages 14
Place of publication Philadelphia, PA United States
Publisher Mosby
Language eng
Formatted abstract

Celiac disease (CeD) is a common gluten-sensitive autoimmune enteropathy. A gluten-free diet is an effective treatment, but compliance is demanding; hence, new treatment strategies for CeD are required.


Parasitic helminths hold promise for treating inflammatory disorders, so we examined the influence of experimental hookworm infection on the predicted outcomes of escalating gluten challenges in CeD subjects.


A 52-week study was conducted involving 12 adults with diet-managed CeD. Subjects were inoculated with 20 Necator americanus larvae, and escalating gluten challenges consumed as pasta were subsequently administered: (1) 10 to 50 mg for 12 weeks (microchallenge); (2) 25 mg daily + 1 g twice weekly for 12 weeks (GC-1g); and (3) 3 g daily (60-75 straws of spaghetti) for 2 weeks (GC-3g). Symptomatic, serologic, and histological outcomes evaluated gluten toxicity. Regulatory and inflammatory T cell populations in blood and mucosa were examined.


Two gluten-intolerant subjects were withdrawn after microchallenge. Ten completed GC-1g, 8 of whom enrolled in and completed GC-3g. Primary outcomes: median villous height-to-crypt depth ratios (2.60-2.63; P = .98) did not decrease as predicted after GC-1g, and the mean IgA-tissue transglutaminase titers declined, contrary to the predicted rise after GC-3g. Secondary outcomes: quality of life scores improved (46.3-40.6; P = .05); celiac symptom indices (24.3-24.3; P = .53), intra-epithelial lymphocyte percentages (32.5-35.0; P = .47), and Marsh scores were unchanged by gluten challenge. Intestinal T cells expressing IFNγ were reduced following hookworm infection (23.9%-11.5%; P = .04), with corresponding increases in CD4+ Foxp3+ regulatory T cells (0.19%-1.12%; P = .001).


Necator americanus and gluten microchallenge promoted tolerance and stabilized or improved all tested indices of gluten toxicity in CeD subjects.
Keyword Celiac disease
Helminth therapy
Mucosal immunology
Regulatory T cells
Intra-epithelial lymphocytes
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1037304
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
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