Insights Gained and Future Outlook From scRNAseq Studies in Autoimmune Rheumatic Diseases

Abstract

Autoimmune rheumatic diseases have a major impact on public health as one of the most common morbidities, and many of these disorders involve both local and systemic manifestations with severe consequences for patient health and quality of life. However, treatment options for many of these diseases remain inadequate for a substantial portion of patients, and progress in developing novel therapeutics has been slow. This lack of progress can be largely attributed to an insufficient understanding of the complex mechanisms driving pathogenesis. Recently, the emergence of single-cell RNA sequencing (scRNAseq) has offered a powerful new tool for interrogating rheumatic diseases, with the potential to assess biological heterogeneity and individual cell function in rheumatic diseases. In this review, we discuss the major insights gained from current scRNAseq interrogations of human rheumatic diseases. We highlight novel cell populations and key molecular signatures uncovered, and also raise a number of hypotheses for follow-up study that may be of interest to the field. We also provide an outlook into two emerging single-cell technologies (repertoire sequencing and spatial transcriptomics) that have yet to be utilized in the field of rheumatic diseases, but which offer immense potential in expanding our understanding of immune and stromal cell behavior. We hope that scRNAseq may serve as a wellspring for the generation and interrogation of novel hypotheses regarding autoreactive lymphocytes and tissue infiltration patterns, and help uncover novel avenues for therapeutic development.

Detecting potential mechanism of vitamin D in treating rheumatoid arthritis based on network pharmacology and molecular docking

“…However, treatment options for many of these diseases remain inadequate for most patients, and progress in developing new treatments has been slow. This lack of progress is attributed mainly to insufficient understanding of the complex mechanisms driving pathogenesis ( Cao et al, 2022 ; Zheng et al, 2022 ).…”

Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus

“…Several review papers have addressed the advantage of spatial transcriptomics in different autoimmune diseases (116,136,138,140). The development of disease pathology Atlases based on bulk RNAseq, scRNAseq, and spatial transcriptomics, machine learning models, and the use of AI to combine clinical and multiomics data, will be crucial in the future research on chronic autoimmune diseases including SLE.…”

Single cell Transcriptome and T cell Repertoire Mapping of the Mechanistic Signatures and T cell Trajectories Contributing to Vascular and Dermal Manifestations of Behcet’s Disease

“…Further technological advances have been made it possible to recover of specific T cell receptor (TCR) and B cell receptor (BCR) sequences in single cells to simultaneously classify the adaptive immune repertoire in complex samples 14 . While these technologies have already been applied to classify immune cell type heterogeneity and T cell clonal behavior in multiple contexts, including cancer 15 , and infection 16 , these tools have yet to be fully applied in the context of autoimmunity and rheumatologic disorders such as BD 17 . In this manuscript, we utilize scRNAseq and scTCRseq to map for the first time the immune cell types present in peripheral circulation and inflamed skin of patients with BD.…”