Abstract
In our paper, we discuss how the early phases of ankylosing spondylitis (AS) are linked to peri-firbocartilagenous osteitis in the sacroiliac joint and entheseal bone related anchoring sites. This skeletal proclivity is linked to an abnormal immunological response to skeletal biomechanical stress and associated microdamage. A key event in the early stages of AS appears to be the association with subclinical Crohn's-like colitis with this gut inflammation being pivotal to the osteitis reaction. Whether this osteitis is consequent to non-specific intestinal innate immune activation or adaptive immune responses against specific microbiotal or self-antigens is unknown. Recurrent iritis is an HLA-B27 associated feature that may predate AS and pursues a course independent of joint involvement, and points toward the pivotal role of organ specific immunology over generalized systemic immune responses in disease expression. Human genetics and animal model studies strongly incriminate the IL23/17 axis and TNF-α in disease pathogenesis. Preliminary work shows a strong convergence of innate immune cells including type 3 innate lymphoid-cells (ILC3) and γδ T-cells in skin, gut, entheseal, and eye inflammation. Despite the HLA-B27 association, the role of adaptive immunity, especially CD8+ T-cells mediated responses remains unproven and alternative theories have been proposed. The emerging non-dependence of axial inflammation on IL-23 but dependence on IL-17A is an unexpected new twist that awaits full explanation. In this mini-review, we discuss the key events in the early stages of human AS from clinical and basic science aspects, which could be crucial for attempted disease prevention studies in at risk subjects.
Highlights
Ankylosing spondylitis (AS) is the prototype of the inflammatory rheumatic diseases grouped under the term spondyloarthritis (SpA) and represents the end phenotype of the axial SpA group [1]
The diagnosis of ankylosing spondylitis (AS) is determined according to the New York criteria with the earlier pre-radiographic phases of AS defined by the ASAS (Assessment of Spondylo-Arthritis International Society) [6, 7], we will focus on these pre-radiographic phases since they may culminate in frank AS
We focused on the early phases of AS, where skeletal mechanical responses to stress and gut dysfunction, whether related to the microbiome, or specific microbes or intrinsic barrier or mucosal immune dysfunction are important
Summary
Ankylosing spondylitis (AS) is the prototype of the inflammatory rheumatic diseases grouped under the term spondyloarthritis (SpA) and represents the end phenotype of the axial SpA group [1]. The diagnosis of AS is determined according to the New York criteria with the earlier pre-radiographic phases of AS defined by the ASAS (Assessment of Spondylo-Arthritis International Society) [6, 7], we will focus on these pre-radiographic phases since they may culminate in frank AS This early phase of disease includes nrAxSpA which may be evident on MRI assessment and includes the events that predate the MRI lesions. Other factors contributing to the difficulty in studying the early phases of AS is the failure to recognize inflammatory back pain, and the absence of visible swelling and often normal inflammatory markers
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