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Etude de la biologie des lymphocytes B et du mécanisme d'action du vedolizumab dans la rectocolite hémorragique et au cours de l'infection chronique à VIH

Abstract : Ulcerative Colitis (UC) is an inflammatory bowel disease (IBD) that leads to chronic inflammation of the rectum and the colon. Even though it is commonly accepted that it results from an exaggerated immune response toward the gut microbiota, the pathophysiology is still not fully understood. Among immune defects, many evidences exist supporting a disturbed B cell system, including the presence of (auto-)antibodies and the infiltration of the lamina propria by plasma cells. Using multiple advanced techniques including single-cell RNA sequencing and single-cell BCR sequencing we extensively characterized the B cell compartment in the blood and the intestinal mucosa of UC patients. We found that the colonic plasma cells phenotype was skewed toward an increased expression of IgG and IgA1 and an increased proportion of short-lived plasma cells. This increased turnover was reflected in the blood by the expansion of ?7+ plasmablasts, which correlated with disease activity and predicted disease course. Our second work focused on the mechanism of action of vedolizumab, a monoclonal antibody targeting the ?4?7 integrin, for both IBD and HIV. In a unique cohort of patients with concomitant IBD and HIV, we unexpectedly found that memory T cells within the lamina propria were not significantly affected. Conversely, lymphoid aggregates, mostly in the terminal ileum were massively impacted. These findings are being further explored and may change the paradigm regarding the mechanism of action of vedolizumab.
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https://tel.archives-ouvertes.fr/tel-03028816
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Submitted on : Friday, November 27, 2020 - 5:34:13 PM
Last modification on : Tuesday, September 28, 2021 - 5:15:44 PM
Long-term archiving on: : Sunday, February 28, 2021 - 8:32:05 PM

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  • HAL Id : tel-03028816, version 1

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Mathieu Uzzan. Etude de la biologie des lymphocytes B et du mécanisme d'action du vedolizumab dans la rectocolite hémorragique et au cours de l'infection chronique à VIH. Sciences agricoles. Université de Paris, 2019. Français. ⟨NNT : 2019UNIP7065⟩. ⟨tel-03028816⟩

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