Vitamin D Is Associated with α4ß7+ Immunophenotypes and Predicts Vedolizumab Therapy Failure in Patients with Inflammatory Bowel Disease.
J Crohns Colitis
; 15(12): 1980-1990, 2021 Dec 18.
Article
en En
| MEDLINE
| ID: mdl-34180967
ABSTRACT
BACKGROUND AND AIMS:
Vitamin D downregulates the in vitro expression of the gut-tropic integrin α4ß7 on immune cells. The clinical relevance of this finding in patients with inflammatory bowel disease [IBD] is unclear. We tested the hypothesis that vitamin D is associated with α4ß7 immunophenotypes and risk of vedolizumab [anti-α4ß7] failure in IBD.METHODS:
We performed single-cell immunophenotyping of peripheral and intestinal immune cells using mass cytometry [CyTOF] in vedolizumab-naïve patients with IBD [N = 48]. We analysed whole-genome mucosal gene expression [GSE73661] from GEMINI I and GEMINI long-term safety [LTS] to determine the association between vitamin D receptor [VDR] and integrin alpha-4 [ITGA4] and beta-7 [ITGB7] genes. We estimated the odds of vedolizumab failure with low pre-treatment vitamin D in a combined retrospective and prospective IBD cohort [N = 252] with logistic regression.RESULTS:
Immunophenotyping revealed that higher 25[OH]D was associated with decreased α4ß7+ peripheral blood mononuclear cells [R = -0.400, p <0.01] and α4ß7+ intestinal leukocytes [R = -0.538, p = 0.03]. Serum 25[OH]D was inversely associated with α4ß7+ peripheral B cells and natural killer [NK] cells and α4ß7+ intestinal B cells, NK cells, monocytes, and macrophages. Mucosal expression of VDR was inversely associated with ITGA4 and ITGB7 expression. In multivariate analysis, 25[OH]D <25 ng/mL was associated with increased vedolizumab primary non-response during induction (odds ratio [OR] 26.10, 95% confidence interval [CI] 14.30-48.90, p <0.001) and failure at 1-year follow-up [OR 6.10, 95% CI 3.06-12.17, p <0.001].CONCLUSIONS:
Low serum 25[OH]D is associated with α4ß7+ immunophenotypes and predicts future vedolizumab failure in patients with IBD. PODCAST This article has an associated podcast which can be accessed at https//academic.oup.com/ecco-jcc/pages/podcast.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vitamina D
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Fármacos Gastrointestinales
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Enfermedades Inflamatorias del Intestino
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Integrinas
/
Anticuerpos Monoclonales Humanizados
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
J Crohns Colitis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos