What do we know about co-stimulatory and co-inhibitory immune checkpoint signals in ankylosing spondylitis?

Ankylosing spondylitis is the main entity of a family of inflammatory diseases affecting many musculoskeletal (sacroiliac joints, spine, and peripheral joints) and extra-musculoskeletal sites, termed spondyloarthritis. While it is debated whether disease onset is primarily driven by autoimmune or autoinflammatory processes, what is certain is that both innate and adaptive immune responses orchestrate local and systemic inflammation, which leads to chronic pain and immobility. Immune checkpoint signals are one key player in keeping the immune system in check and in balance, but their role in disease pathogenesis is still rather elusive. Therefore, we ran a MEDLINE search utilizing the PubMed platform for a variety of immune checkpoint signals in regard to ankylosing spondylitis. In this review, we summarize the experimental and genetic data available and evaluate the relevance of immune checkpoint signalling in the pathogenesis of ankylosing spondylitis. Markers such as PD-1 and CTLA-4 have been extensively studied and facilitate the concept of an impaired negative immune regulation in ankylosing spondylitis. Other markers are either neglected completely or insufficiently examined, and the data is conflicting. Still, some of those markers remain interesting targets to decipher the pathogenesis of ankylosing spondylitis and to develop new treatment strategies.