Nature versus nurture in the spectrum of rheumatic diseases: Classification of spondyloarthritis as autoimmune or autoinflammatory

Spondyloarthritides (SpA) include inflammatory joint diseases with various clinical phenotypes that may also include the axial skeleton and/or entheses. SpA include psoriatic arthritis, reactive arthritis, enteropathic arthritis and ankylosing spondylitis; the latter is frequently associated with extra-articular manifestations, such as uveitis, psoriasis, and inflammatory bowel disease. SpA are associated with the HLA-B27 allele and recognize T cells as key pathogenetic players. In contrast to other rheumatic diseases, SpA affect women and men equally and are not associated with detectable serum autoantibodies. In addition, but opposite to rheumatoid arthritis, SpA are responsive to treatment regimens including IL-23 or IL-17-targeting biologics, yet are virtually unresponsive to steroid treatment. Based on these differences with prototypical autoimmune diseases, such as rheumatoid arthritis or connective tissue diseases, SpA may be better classified among autoinflammatory diseases, with a predominant innate immunity involvement. This would rank SpA closer to gouty arthritis and periodic fevers in the spectrum of rheumatic diseases, as opposed to autoimmune-predominant diseases. We herein provide available literature on risk factors associated with SpA in support of this hypothesis with a specific focus on genetic and environmental factors.