Tu122 - Complex Pathogenesis of Axial Spondyloarthritis: Involvement of Type 1 Interferon Revealed by Single-cell RNA Sequencing

Abstract Text: [Background] Spondyloarthritis (SpA) is a group of chronic inflammatory diseases that is characterized by primarily affecting the entheses and synovial joints. There is overlap among the diseases that comprise SpA and diversity of symptoms within the same disease, demanding stratification by immunophenotype. In this study, we aimed to reveal the relation between immunophenotype and axial lesions in SpA patients.
[Methods] We recruited 77 patients with SpA, including psoriatic arthritis, axial SpA (axSpA), pustulotic arthro-osteitis. The scRNA-seq data on peripheral blood mononuclear cells and clinical information were integrally analysed.
[Results] The presence of axial lesions was significantly associated with high abundance of plasmacytoid dendritic cells (pDCs, P < 0.001, OR = 2.28). Cell-cell interaction analysis revealed that pDCs had intensive signal to CD8+ T cells and myeloid DCs (mDCs) in HLA-B27-positive cases. In contrast, HLA-B27-negative cases did not exhibit this interaction, and a significant association between disease activity and CD4+ T cells characterized by high interferon-stimulated genes (ISG) was revealed (P < 0.001, OR = 2.01). pDCs were one of the major sources of type I interferon and could stimulate CD4+ T cells.
[Conclusion] scRNA-seq analysis demonstrated distinct pathological profiles of axSpA based on HLA-B27 status. In HLA-B27-positive patients, pDCs appeared to facilitate the activation of mDCs and CD8+ T cells, whereas in HLA-B27-negative patients, pDCs were suggested to produce type I interferon and stimulate CD4+ T cells. Stratifying patients by HLA-B27 status and targeting type I interferon in HLA-B27-negative cases could enhance the development of precision medicine.