The following is a summary of “Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis,” published in the November 2023 issue of Rheumatology by Tavasolian et al.
Recent genomic and proteomic advances offer new insights into ankylosing spondylitis (AS) biology and potential targets for diagnosis and management. Researchers performed a retrospective study to comprehensively profile the proteome and miRNA of plasma-derived exosomes in AS.
Plasma samples from AS patients and healthy controls (HC) were isolated through ultracentrifugation. These samples were then analyzed using extracellular vesicle flow cytometry to characterize exosome surface markers through a multiplex immunocapture assay. The study included cytokine profiling of plasma-derived exosomes and cell culture supernatants. To identify miRNA populations in exosomes from plasma fractions, next-generation sequencing was utilized. The analysis involved sorting CD4+ T cells and analyzing the frequency and proliferation of CD4+ T-cell subsets following treatment with AS-exosomes, assessed through flow cytometry.
The study demonstrated higher expression of exosome marker proteins CD63 and CD81 in AS patients compared to HC (q<0.05). Plasma-derived AS-exosomes showed decreased levels of interleukin (IL)-8 and IL-10 (q<0.05). When AS-exosomes were co-cultured with HC CD4+ T cells, it led to a significant upregulation of IFNα2 and IL-33 (q<0.05). Exosomes from AS patients inhibited the proliferation of regulatory T cells (Treg), providing insight into the mechanism of chronically activated T cells in this condition. Furthermore, exposure of CD4+ T cells from healthy individuals to AS-exosomes reduced the proliferation of FOXP3+ Treg cells and decreased the frequency of FOXP3+IRF4+ Treg cells. miRNA sequencing identified 24 differentially expressed miRNAs in circulating exosomes of AS patients compared to HC, with 22 upregulated and 2 downregulated.
The study found exosome profiles differ in AS patients, suggesting a role in disease pathogenesis.