Gaetano Iaquinto, MD1, Vera Rotondi Aufiero, PhD2, Giuseppe Mazzarella, PhD3, Giovanni De Chiara, MD4, Valentina Tenneriello, 4 1S. Rita Hospital, Atripalda, Campania, Italy; 2Institute of Food Science, National Research Council, Avellino, Campania, Italy; 3Institute of Food Sciences-CNR, Avellino, Campania, Italy; 4AORN San G. Moscati Hospital, Avellino, Campania, Italy
Introduction: In Celiac Disease (CeD), IL-15 affects the epithelial barrier by acting on intraepithelial lymphocytes, promoting interferon γ (IFN-γ) production, eliciting apoptotic death of enterocytes by the Fas/Fas ligand system, as well as by inducing strong cytotoxic activity.Moreover, IL-15 has been shown to impair the immunoregulatory mechanisms.
In this study we investigated the effects of a monoclonal antibody neutralizing human IL-15 (anti IL-15) in active CeD patients, by using an organ culture system.
Methods: Duodenal biopsies obtained from 10 patients with untreated CeD were cultured in vitro with or without anti IL-15 antibody. The expression of CD95/Fas, HLA-E and perforin, in the surface epithelium, were analyzed by immunohistochemistry.
Total RNA was extracted from frozen section of in vitro cultured biopsy samples, and relative expression of IFN-γ and TGF-β cytokines was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR).
Results: Biopsies cultured with anti IL-15 antibody showed a reduction of expression of Fas, perforin and HLA-E in the surface epithelium, compared to biopsies cultured in medium alone.
A trend to downregulation of IFN- γ and upregulation of TGF-β was observed in biopsies incubated with anti IL-15, compared to medium alone.
Discussion: Our data suggest that the neutralizing effect of anti IL-15 antibody in CeD could block abnormal apoptosis, downregulating the expression of Fas and HLA-E as well as the release of cytotoxic proteins, such as perforin.
Furthermore, the anti IL-15 antibody is able to dampen the hyperactive immune response by reducing IFN-γ and increasing TGF-β expression.
Overall, IL-15 appears to be a very promising candidate for therapeutic intervention in CeD patients.
Disclosures:
Gaetano Iaquinto indicated no relevant financial relationships.
Vera Rotondi Aufiero indicated no relevant financial relationships.
Giuseppe Mazzarella indicated no relevant financial relationships.
Giovanni De Chiara indicated no relevant financial relationships.
Valentina Tenneriello indicated no relevant financial relationships.
Gaetano Iaquinto, MD1, Vera Rotondi Aufiero, PhD2, Giuseppe Mazzarella, PhD3, Giovanni De Chiara, MD4, Valentina Tenneriello, 4. P3207 - IL-15 Neutralizing Antibody Inhibits Cytotoxic T Cell-Mediated Tissue Damages and Increases TGF-Beta Expression in Celiac Disease, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
