Innate Defense-Antigen Presentation Coupling Patterns revealed by Single-immunocyte Transcriptomics Contributes to the Onset and Prognoses of Ankylosing Spondylitis

Background Ankylosing spondylitis (AS) is an autoimmune disease causing severe deformities and the immunological patterns associated with AS occurrence and development were unknown. Methods After recruiting healthy donors and patients in the early, disabled and remission stages, we performed single-cell RNA sequencing for PBMCs to investigate the cytotaxonomic and immunological hallmarks associated with AS onset, aggravation and remission and explore the intrinsic laws causing AS lesions. Results The innate defense functions including antibacterial peptide production, bacterial lipoprotein response and type-III IFN production for most cell types and cell abundance of cytotoxic NK subsets were overall augmented with onset and negatively correlated with AS severity. Endogenous antigen presentation in B, plasma B and plasmacytoid dendritic cells increased during onset and exogenous antigen presentation of NK subset characterized as antigen-presenting cells (APC-NK) were enhanced with aggravation; but the above functions weakened with remission. APC-NK abundance and their presentation scores were globally negatively correlated with cytotoxic NK abundance and innate-defense scores for multiple cell types. CD4+ effector T-cell abundance and -mediated cytotoxicity, the promotion of HLA-DRB1+ NK cells on CD4+ T-cell proliferation and cytotoxicity, and HLA-DPB1/DPA1 levels of APC-NK were all associated with AS severity. HLA-DPB1/DPA1 levels in HLA-DRB1+ NK cells both contributed to CD4+ T-cell parameters. Conclusions Our study depict a landscape for the dynamic features of AS onset and prognoses; this unmasks a biological law for AS lesions that innate defense-antigen presentation signaling drives AS pathogenesis and the trade-off between innate defense and NK-dependent exogenous antigen presentation contributes to different prognoses.