RT Journal Article
SR Electronic
T1 Identification of biomarkers of response to abatacept in patients with SLE using deconvolution of whole blood transcriptomic data from a phase IIb clinical trial
JF Lupus Science & Medicine
FD Lupus Foundation of America
SP e000206
DO 10.1136/lupus-2017-000206
VO 4
IS 1
A1 Somnath Bandyopadhyay
A1 Sean E Connolly
A1 Omar Jabado
A1 June Ye
A1 Sheila Kelly
A1 Michael A Maldonado
A1 Rene Westhovens
A1 Peter Nash
A1 Joan T Merrill
A1 Robert M Townsend
YR 2017
UL http://lupus.bmj.com/content/4/1/e000206.abstract
AB Objective 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.Methods 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.Results 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).Conclusions 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.Trial registration number NCT00119678; results.