Abstract

OBJECTIVE:

The spondyloarthropathies, including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and arthritis associated with inflammatory bowel disease, cause chronic inflammation of large peripheral and axial joints, eyes, skin, ileum and colon. Genetic studies reveal common candidate genes for ankylosing spondylitis, psoriatic arthritis and Crohn's disease, including IL23R, IL12B, STAT3 and Card9, associated with IL-23 signaling downstream of the dectin-1 β-glucan receptor. In autoimmune-prone SKG mice with mutated ZAP-70, which attenuates T cell receptor signaling and increases the autoreactivity of T cells in the peripheral repertoire, IL-17-dependent inflammatory arthritis developed after dectin-1-mediated fungal infection. We determined whether SKG mice injected with 1,3-D β-glucan (curdlan) develop evidence of SpA, and the relationship of innate and adaptive autoimmunity to this process.

METHODS:

SKG mice and control BALB/c mice were injected once with curdlan or mannan. Arthritis was scored weekly and organ pathology was determined. Anti-IL-23 mAb were injected into curdlan-treated SKG mice. CD4(+) T cells were transferred from curdlan-treated to SCID mice and sera were analyzed for autoantibodies.

RESULTS:

After systemic injection of curdlan, SKG mice developed enthesitis, wrist, ankle and sacro-iliac arthritis, dactylitis, plantar fasciitis, vertebral inflammation, ileitis resembling Crohn's disease, and unilateral uveitis. Mannan triggered spondylitis and arthritis. Arthritis and spondylitis were T cell and IL-23-dependent and could be transferred to SCID recipients with CD4(+) T cells. Spondyloarthritis was associated with collagen and proteoglycan-specific autoantibodies. Conclusion: The SKG ZAP-70(W163C) mutation predisposes BALB/c mice to spondyloarthropathy after systemic β-glucan or mannan exposure resulting from innate and adaptiveautoimmunity.

Copyright © 2012 by the American College of Rheumatology.