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• W2740449441 endingPage "e000206" @default.
• W2740449441 startingPage "e000206" @default.
• W2740449441 abstract "To characterise patients with active SLE based on pretreatment gene expression-defined peripheral immune cell patterns and identify clusters enriched for potential responders to abatacept treatment.This post hoc analysis used baseline peripheral whole blood transcriptomic data from patients in a phase IIb trial of intravenous abatacept (~10 mg/kg/month). Cell-specific genes were used with a published deconvolution algorithm to identify immune cell proportions in patient samples, and unsupervised consensus clustering was generated. Efficacy data were re-analysed.Patient data (n=144: abatacept: n=98; placebo: n=46) were grouped into four main clusters (C) by predominant characteristic cells: C1-neutrophils; C2-cytotoxic T cells, B-cell receptor-ligated B cells, monocytes, IgG memory B cells, activated T helper cells; C3-plasma cells, activated dendritic cells, activated natural killer cells, neutrophils; C4-activated dendritic cells, cytotoxic T cells. C3 had the highest baseline total British Isles Lupus Assessment Group (BILAG) scores, highest antidouble-stranded DNA autoantibody levels and shortest time to flare (TTF), plus trends in favour of response to abatacept over placebo: adjusted mean difference in BILAG score over 1 year, -4.78 (95% CI -12.49 to 2.92); median TTF, 56 vs 6 days; greater normalisation of complement component 3 and 4 levels. Differential improvements with abatacept were not seen in other clusters, except for median TTF in C1 (201 vs 109 days).Immune cell clustering segmented disease severity and responsiveness to abatacept. Definition of immune response cell types may inform design and interpretation of SLE trials and treatment decisions.NCT00119678; results." @default.
• W2740449441 created "2017-08-08" @default.
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• W2740449441 date "2017-07-01" @default.
• W2740449441 modified "2023-10-18" @default.
• W2740449441 title "Identification of biomarkers of response to abatacept in patients with SLE using deconvolution of whole blood transcriptomic data from a phase IIb clinical trial" @default.
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• W2740449441 doi "https://doi.org/10.1136/lupus-2017-000206" @default.
• W2740449441 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5704740" @default.
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