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). pp. 508-516.

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Abstract

BACKGROUND: 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.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: Two gluten-intolerant subjects were withdrawn after microchallenge.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).

CONCLUSIONS: Necator americanus and gluten microchallenge promoted tolerance and stabilized or improved all tested indices of gluten toxicity in CeD subjects.

Item ID: 35973
Item Type: Article (Research - C1)
ISSN: 1097-6825
Keywords: Celiac disease; gluten; hookworm; autoimmunity; helminth therapy; desensitization; mucosal immunology; regulatory T cells; intra-epithelial lymphocytes gluten; hookworm; autoimmunity; helminth therapy; desensitization; mucosal immunology; regulatory T cells; intra-epithelial lymphocytes
Date Deposited: 16 Jun 2015 00:50
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110307 Gastroenterology and Hepatology @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110703 Autoimmunity @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 75%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 25%
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