Colorectal polyps from pediatric patients sensitizied to cow´s milk showed elevated pro-inflamatory mediators, IgE-expressing cells and IgE memory B lymphocytes

MANUELA ILID; JULIÁN VACCARO; EMANUEL FEREGOTTI; MARÍA BELEN POLO; MELISA MONCADA; LORENA MENENDEZ; PAULA BOROBIA; CECILIA ZUBIRI; ANABELA ZOSI; VIVIANA BERNEDO; LUCIANA GUZMÁN; MARCELA GARCIA; EUGENIA M ALTAMIRANO; RENATA CURCIARELLO; CECILIA MUGLIA; GUILLERMO DOCENA

Mar del Plata

Congreso; Reunión Biociencias 2022; 2022

SAIC SAI SAFIS

Cow's milk allergy (CMA) is caused by an immune response to food dairy proteins and is mainly observed in the pediatric population. We previously described that colorectal polyps in children with CMA present an allergic cell infiltrate rich in eosinophils, Th2 inflammatory environment and germinal centers with IgE-producing cells. In this work, we aimed to get further insights on the inflammatory mechanisms that may contribute to polyp development and search for IgE memory B cells (IgE LBmem). Juvenile polyps (n=23) were removed by colonoscopy followed by epithelial and stromal cell isolation. Surrounding control tissue (SCT) biopsies and peripheral blood were also obtained in every patient. Immunofluorescence was performed to evaluate IL-33 and TSLP production (n=8); IL-1β, IL-33, TLSP and CCL26 expression was quantified by RT-qPCR (n=10); the frequency of eosinophils (CD45+, CD14-, CD16-, Siglec8+), IgE-expressing cells (IgE+), and IgE+ LBmem (CD19+, CD27+, CD138-, IgD-, IgE+) was determined by flow cytometry (n=10). We found IL-33+ and TSLP+ epithelial cells by confocal microscopy and a significant increase of IL-1β transcripts in polyp tissue compared to SCT (p=0,031), especially in the epithelial compartment (p=0,034). Similarly, IL-33 was higher in polyps than SCT (p=0,057), while TSLP and CCL26 expression was variable in different polyps and SCT. Concordantly, we found an eosinophil-dominant cell infiltration in polyps (1,55+/-2,79% of live cells) with IgE+ cells (35,41+/-20,36% of the total cells). Remarkably, IgE+ LBmem cells were observed within polyps and higher than in peripheral blood (20+/-2 vs 12+/-2% of LBmem cells, respectively, p=0,051). In conclusion, our results suggest that juvenile colorectal polyp tissue from cow's milk sensitized children produce proinflammatory signals that trigger a Th2 environment, favoring eosinophil recruitment, IgE production and LB differentiation to IgE+LBmem+ cells. This is the first report of the presence of human colonic IgEmem+ B cells in food allergy.