Baseline Peripheral Blood Mononuclear Cell Transcriptomics Before Ustekinumab Treatment Is Linked With Crohn's Disease Clinical Response at 1 Year.
Clin Transl Gastroenterol
; 14(12): e00635, 2023 12 01.
Article
en En
| MEDLINE
| ID: mdl-37655708
ABSTRACT
INTRODUCTION:
Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin (IL)-12 and IL-23, is used for Crohn's disease (CD), and the documented clinical remission rate after 1 year was observed in approximately 50% of patients. We aimed to identify predictors for a clinical response using peripheral blood obtained from patients with CD just before ustekinumab treatment initiation.METHODS:
RNA extraction from peripheral blood mononuclear cells was followed by mRNA paired-end sequencing. Differential gene expression was performed using DESeq2.RESULTS:
We processed samples from 36 adults with CD (13 men, 36%) obtained at baseline before starting ustekinumab treatment. Twenty-two of 36 (61%) were defined as responders and 14/36 (39%) as nonresponders after 1 year based on Physician Global Assessment. Differential gene expression between responders (n = 22) and nonresponders (n = 14) did not show a gene expression signature that passed false discovery rate (FDR) correction. However, the analyses identified 68 genes, including CXCL1/2/3, which were induced in nonresponders vs responders with P < 0.05 and fold change above 1.5. Functional annotation enrichments of these 68 genes using ToppGene indicated enrichment for cytokine activity (FDR = 1.98E-05), CXCR chemokine receptor binding (FDR = 2.11E-05), IL-10 signaling (FDR = 5.03E-07), genes encoding secreted soluble factors (FDR = 1.73E-05), and myeloid dendritic cells (FDR = 1.80E-08).DISCUSSION:
No substantial differences were found in peripheral blood mononuclear cell transcriptomics between responders and nonresponders. However, among the nonresponders, we noted an increased inflammatory response enriched for pathways linked with cytokine activity and chemokine receptor binding and innate myeloid signature. A larger cohort is required to validate and further explore these findings.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Crohn
/
Ustekinumab
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Humans
/
Male
Idioma:
En
Revista:
Clin Transl Gastroenterol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Israel