Single-cell transcriptome sequencing analysis of peripheral blood mononuclear cells reveals immune signatures in patients with polymyalgia rheumatica
TL;DR
Functional enrichment analysis showed that the co-stimulation, cytotoxicity, antigen processing and presentation, and inflammation promotion of various immune cells in PMR patients were all enhanced.
Abstract
Polymyalgia rheumatica (PMR) is an auto-inflammatory disease or autoimmune disease that involves multiple immune cells. In this study, single-cell transcriptome sequencing (scRNA-seq) combined with cellular communication analysis were used to investigate immune characteristics of peripheral blood mononuclear cells (PBMCs) in PMR patients. Three newly diagnosed PMR patients were recruited; their PBMCs were isolated and sequenced on the Illumina NovaSeq 6000 sequencing platform. The PBMCs scRNA-seq data of three normal controls were downloaded from the 10× Genomics platform for joint analysis. Relative to healthy controls, PMR patients exhibited a reduced abundance of circulating T cells, alongside an expanded megakaryocyte/platelet compartment. At the T cell subset level, PMR was associated with an increased proportion of pro-inflammatory KIR + NK-like T cells, while CD4 + central memory T cells, effector memory T cells, and Th1 cells showed reductions in relative abundance. Circulating NK cell subsets were disproportionately represented in PMR patients; notably, the CD56 dim CD16 hi -ISG subset was exclusively detected in PMR cases. While no statistically meaningful shifts were observed in the global proportional distribution of B cells, the unswitched memory B cell compartment was absent in PMR patients. Multiple monocyte subsets annotated for elevated inflammatory and interferon-stimulated gene signatures, including CD14_Monocyte-ISG and CD16_Monocyte-IFITM1, were uniformly expanded in the PMR cohort. Functional enrichment analysis showed that the co-stimulation, cytotoxicity, antigen processing and presentation, and inflammation promotion of various immune cells in PMR patients were all enhanced. Key inflammatory pathways were widely activated, including the interferon-γ signaling pathway, interleukin-1β production, and NK cell-mediated cytotoxicity. Cellular communication analysis revealed more interactions but slightly weaker strength in PMRs, with increased communication in TGF-β and CD48 pathways. This preliminary study may help to further elucidate the pathogenesis of PMR and provide a theoretical basis for identifying diagnostic markers and discovering new therapeutic targets.