Single-Cell Multiomics and Immune Repertoire Features Identify Adalimumab-Sensitive Immune Cells During Ankylosing Spondylitis

Abstract

Objectives: Ankylosing spondylitis (AS) is a chronic, inflammatory condition that particularly affects the spine. Adalimumab, an anti-TNF-α agent, is frequently used to suppress autoimmune responses in patients with active AS; however, the immune cell subsets change and their states during the course of AS remain unknown. In the present study, we aimed to comprehensively estimate the single-cell level transcriptional changes in peripheral blood mononuclear cells (PBMCs) after adalimumab treatment in the AS patient. Methods: A droplet-based platform was used to perform single-cell multiomics sequencing of PBMCs obtained from patients during the pre-adalimumab or post-adalimumab treatment phase. Multiomics analysis, including single-cell level unbiased transcriptome, surface protein expression (CITE-seq), and T cell receptor repertoire, was performed using the single-cell omics data from the AS patient. Results: TNF-alpha-induced genes, such as Egr1 and FOS, were remarkably decreased after treatment with adalimumab via single-cell profiling of monocytes, which demonstrated the comprehensive impact of adalimumab treatment. Dominant T-cell clonotypes with paired alpha and beta chains, such as the TRAV13-2/TRBV6-5 clones, were identified in patients with AS before adalimumab treatment. Conclusions: Our findings demonstrate the feasibility of applying single-cell level multiomics to identify the detailed inflammatory immune signatures of AS in response to adalimumab. Furthermore, comparative analysis predicted that most differentially expressed genes before and after treatment could potentially be used as novel candidate target genes, which may be beneficial for the AS patient. Funding Statement: Ministry of Science and Technology (MOST-107-2314-B-009-005-MY2, MOST-109-2314-B-009-003-MY3), Center For Intelligent Drug Systems and Smart Bio-devices (IDS2B) of National Chiao Tung University in Taiwan, and University System of Taiwan Joint Research Program (VGHUST108-G2-2-1, VGHUST109-V2-1-2) for their support. Declaration of Interests: None declared. Ethics Approval Statement: This investigation (CE19024B) was approved by the Institutional Review Board and the Ethics Committee of the Taichung Veterans General Hospital, Taichung, Taiwan. Written informed consent was obtained from the subjects or their family members in accordance with the institutional requirements and Declaration of Helsinki principles.