GALECTIN-1 EXPRESSION DELINEATES RESPONSE TO TREATMENT IN CELIAC DISEASE PATIENTS AND SUGGESTS A POTENTIAL NOVEL THERAPEUTIC TARGET.

JULIO C. BAI ; ROBERTO M. MAZURE; HORACIO VÁZQUEZ; LUCIANO MOROSI ; GABRIEL A. RABINOVICH; KARINA MARIÑO; MARÍA LAURA MORENO; ANA M. CABANNE4, ; AMADO A. QUINTAR; CRISTINA A. MALDONADO; EDUARDO MAURIÑO; EDGARDO SMECUOL; SONIA NIVELONI; SUNDBLAD, VICTORIA

Washington

Congreso; Digestive Disease Week; 2018

American Gastroenterology Association

In celiac disease (CD), intolerance to indigestible wheat gluten peptides results in chronic intestinal inflammation associated with an extensive Th1 and Th17 responses. Compelling evidence highlights a major role for galectins (Gal), a family of lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates,in controlling innate and adaptive immune responses. While,Gal-1 is mainly produced in the lamina propria (LP), Gal-2, -3, -4, -7 and -9 are constitutively expressed within the epithelial compartment of the intestines. Galectin-1 is widely expressed in inflammatory macrophages, tolerogenic DCs, Tregs and intestinal epithelial cells. Despite of the critical immunoregulatory activities of Gal, no studies have been conducted to elucidate their role in gut immune homeostasis and intestinal inflammation of CD patients.Aim: to assess the expression of this Gal-1 in biopsies of CD patients before and after gluten withdrawal.Methods: Gal-1 expression was evaluated by immunohistochemistry in duodenal biopsies from untreated CD patients (n= 10), gluten-free diet treated CD patients (GFD-CD)(n= 10) and control subjects (n= 10). Gal-1 expression was assessed by immunohistochemistry using a rabbit anti-Gal-1 or anti-Gal-4 polyclonal antibodies (dilution 1:400) as described and a horseradish peroxidase-conjugated anti-rabbit IgG (dilution 1:1000; Amersham; GE Healthcare, Little Chalfont, UK) as a secondary antibody (Vectastain Elite ABC kit).To further characterize the underlying inflammatory response and given the association of Gal-1 with induction of Foxp3+Tregs, we analyzed the expression of this transcription factor in inflammatory infiltrates.Results: Biopsies from controls showed moderate stromal and epithelial Gal-1 staining, whereas both epithelia and stroma from untreated CD patients were poorly labeled. Biopsies from GFD-CD patients showed a dramatic increase in Gal-1, but not Gal-4, immunoreactivity (p