Ankylosing spondylitis: From pathogenesis to therapy

Int Immunopharmacol. 2025 Jan 3:145:113709. doi: 10.1016/j.intimp.2024.113709. Epub 2024 Dec 6.

Abstract

Ankylosing spondylitis (AS) is an autoimmune rheumatic disease that primarily affects the axial joints, with its etiology complex and still not fully understood. The unknown pathogenesis of AS limits the development of treatment strategies, so keeping up-to-date with the current research on AS can help in searching for potential therapeutic targets. In addition to the classic HLA-B27 genetic susceptibility and Th17-related inflammatory signals, increasing research is focusing on the influence of autoantigen-centered autoimmune responses and bone stromal cells on the onset of AS. Autoantigens derived from gut microbiota and preferential TCR both exacerbate the autoimmune response in patients with AS. Furthermore, dysregulated bone metabolism also promotes pathological new bone formation in AS. Current treatments approved for AS almost focus on the management of inflammation with inconsistent treatment results due to the heterogeneity of patients. In this review, we systematically summarized various pathogenesis and management of AS, meanwhile discussed the underlying risk factors and potential therapeutic targets.

Keywords: Ankylosing spondylitis; Pathogenesis; Therapeutic targets; Treatment.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantigens / immunology
  • Gastrointestinal Microbiome / immunology
  • Genetic Predisposition to Disease
  • HLA-B27 Antigen* / genetics
  • HLA-B27 Antigen* / immunology
  • Humans
  • Spondylitis, Ankylosing* / genetics
  • Spondylitis, Ankylosing* / immunology
  • Spondylitis, Ankylosing* / therapy
  • Th17 Cells / immunology

Substances

  • Autoantigens
  • HLA-B27 Antigen