Pathogenesis of spondyloarthritis
- David T Yu, MD
David T Yu, MD
- Emeritus Professor
- University of California Los Angeles
- Astrid van Tubergen, MD, PhD
Astrid van Tubergen, MD, PhD
- Maastricht University Medical Center
The term spondyloarthritis (SpA, formerly spondyloarthropathy) refers to a group of disorders that includes ankylosing spondylitis (AS), nonradiographic axial SpA (nr-axSpA), undifferentiated spondyloarthritis (USpA), reactive arthritis, and the arthritis and spondylitis that may accompany psoriasis and inflammatory bowel diseases (IBD). SpA can also be differentiated into axial and peripheral SpA, depending upon the predominant regions of involvement. Axial SpA includes both AS and nr-axSpA, based upon the presence or absence, respectively, of abnormalities of the sacroiliac joints on plain radiography.
This topic review will focus primarily on the pathogenesis of AS, regarding which the most is known. The pathogenesis of each of the other members of the SpA family, especially nr-axSpA, is probably closely related to that of AS . The clinical manifestations, diagnosis, and treatment of AS are presented separately. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Assessment and treatment of ankylosing spondylitis in adults".)
The clinical aspects of the other types of SpA are also presented in detail elsewhere, as is SpA in children. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults" and "Reactive arthritis" and "Clinical manifestations and diagnosis of psoriatic arthritis" and "Clinical manifestations and diagnosis of arthritis associated with inflammatory bowel disease and other gastrointestinal diseases" and "Spondyloarthritis in children".)
OVERVIEW OF PATHOGENESIS
Several elements are important in the pathogenesis of spondyloarthritis (SpA), a group of diseases with diverse clinical manifestations, which involve several different structures. These elements include interactions in the context of a particular genetic background between the gut microbiome, innate lymphoid cells, and the anatomic structures that are disease targets. Those structures include, for axial SpA, the entheses along the axial skeleton, and for peripheral SpA, the peripheral joints. At the sites of pathology, the major mediators are tumor necrosis factor (TNF)-alpha and interleukin (IL)-17 and IL-17A. (See 'Proinflammatory mediators validated by clinical observations' below and 'The gut microbiome, gut mucosa, and IL-23' below.)
The largest single genetic contribution is from the gene for human leukocyte antigen (HLA)-B27, but the presence of HLA-B27 is not absolutely essential. Moreover, non-HLA genes and others are also involved. (See 'Genetic factors' below.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- OVERVIEW OF PATHOGENESIS
- PROINFLAMMATORY MEDIATORS VALIDATED BY CLINICAL OBSERVATIONS
- THE GUT MICROBIOME, GUT MUCOSA, AND IL-23
- Presence of mucosal lesions
- SpA-specific gut microbiome and damage of intestinal mucosal barriers
- IL-23 induction by the gut microbiota
- Potential roles of group 3 innate lymphoid cells
- Possible role for IL-23
- GENETIC FACTORS
- Role of HLA-B27
- - Classical (canonical) structure of HLA-B27
- - HLA-B27 as free heavy chains
- - HLA-B27 misfolding and autophagy
- Non-HLA genes
- COEXISTING BONE EROSION AND NEW BONE FORMATION
- INFORMATION FOR PATIENTS