Antonio J Santos

US Patent:

20220221445, Jul 14, 2022

Filed:

Jun 3, 2020

Appl. No.:

17/613430

Inventors:

- Stanford CA, US
Antonio Santos - Palo Alto CA, US

International Classification:

G01N 33/50
C12N 5/0783
C12N 5/071
G01N 33/564

Abstract:

Air-liquid interface organoid cultures are initiated from human small intestine biopsy tissue comprising both the synintestinal epithelium and native intestinal immune cells, without reconstitution, which may be obtained from an individual pre-disposed or suffering from celiac disease. The organoid cultures exhibit T cell activation in response to in vitro gluten challenge and provide tools for a novel diagnostic method for celiac disease. Diagnosis may comprise the addition of immunogenic gluten-derived peptides into the organoid cultures, and assessing hallmarks of active celiac disease, including without limitation: 1) gliadin-presentation, resulting T-cell responses, such as 2) expansion and 3) activation, 4) epithelial-cell death and consequent 5) increased proliferative epithelial cell responses to gliadin. Celiac patients, either in GRD or GFD, test positive for these tests. In other embodiments the organoids are used to test responses to candidate therapeutic agents, assessing reduction of gliadin-dependent (1) T cell activation or expansion, or (2) organoid epithelial cell death.