Format

Send to

Choose Destination
Front Immunol. 2018 Jul 11;9:1603. doi: 10.3389/fimmu.2018.01603. eCollection 2018.

Beneficial Effects of Human Anti-Interleukin-15 Antibody in Gluten-Sensitive Rhesus Macaques with Celiac Disease.

Author information

1
Division of Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
2
PreCliniTria LLC, Mandeville, LA, United States.
3
Division of Veterinary Medicine, Tulane National Primate Research Center, Covington, LA, United States.
4
Division of Clinical Research, Integrated Research Facility, National Institute of Allergy and Infectious Disease, Frederick, MD, United States.
5
Division of Immunology, Tulane National Primate Research Center, Covington, LA, United States.
6
Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.
7
Teva Pharmaceuticals, R&D, Biologics, Lead Antibody Discovery, Sydney, NSW, Australia.

Abstract

Overexpression of interleukin-15 (IL-15) is linked with immunopathology of several autoimmune disorders including celiac disease. Here, we utilized an anti-human IL-15 antibody 04H04 (anti-IL-15) to reverse immunopathogenesis of celiac disease. Anti-IL-15 was administered to six gluten-sensitive rhesus macaques with celiac disease characteristics including gluten-sensitive enteropathy (GSE), and the following celiac-related metrics were evaluated: morphology (villous height/crypt depth ratio) of small intestine, counts of intestinal intraepithelial lymphocytes, IFN-γ-producing CD8+ and CD4+ T cells, plasma levels of anti-gliadin and anti-intestinal tissue transglutaminase IgG antibodies, as well as peripheral effector memory (CD3+CD28-CD95+) T cells. Anti-IL-15 treatment reversed the clinically relevant disease endpoints, intraepithelial lymphocyte counts, and villous height/crypt depth ratios within jejunal biopsies to normal levels (P < 0.001). Additionally, intestinal CD8+ and CD4+ T cell IFN-γ production was reduced (P < 0.05). Extra-intestinally, anti-IL-15 treatment reduced peripheral NK cell counts (P < 0.001), but otherwise, non-NK peripheral lymphocytes including effector memory T cells and serum blood chemistry were unaffected. Overall, providing the beneficial disease-modulatory and immunomodulatory effects observed, anti-IL-15 treatment might be considered as a novel therapy to normalize intestinal lymphocyte function in celiac disease patients with GSE.

KEYWORDS:

antibody therapy; celiac disease; gluten; interleukin-15; small intestine

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center