Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Spondyloarthritis (SpA) encompasses a group of chronic inflammatory conditions involving axial arthritis that includes ankylosing spondylitis (AS). GWAS studies in AS have implicated multiple genes regulating the development and activity of Th17 cells. IL23, a cytokine required for driving the pathogenicity of Th17 cells, is sufficient to cause spondylitis-like pathology in mice. Thus, excessive production of IL-23 in response to environmental stimuli might predispose towards the development of SpA. The aim of this study was to determine if macrophages from SpA patients produce excess inflammatory cytokines (including IL-23) in response to different pattern-recognition receptor (PRR) agonists.
Methods:
Monocytes isolated by CD14 magnetic beads from 12 AS, 12 non-AS SpA, and 12 control subjects were differentiated into macrophages with M-CSF. Macrophages were stimulated with LPS (TLR4), CL097 (TLR7/8), PGN (TLR2), and Curdlan (Dectin-1) and IL6, IL8, IL10, IL23, and TNF-α quantitated by Luminex Multiplex assay or ELISA. Comparisons between groups were conducted using analysis of variance with adjustment for multiple comparisons. Subgroup analyses were conducted for sex, current TNF-blocker, presence of axial disease, and HLA-B27.
Results:
Subjects: AS and SpA patients differed in HLA-B27 positivity (92% vs. 42% respectively, p=0.027), current biologic therapy (25% vs. 67%, p=0.041) and axial disease (100% vs. 50%, p=0.014). Cytokine results: No differences were observed for IL-10. AS macrophages produced more IL-8 than controls in response to PGN (p=0.017). LPS stimulated comparably elevated IL-6 by both AS and SpA macrophages (p≥0.029). AS and SpA cells produced comparably increased TNF-α in response to LPS and PGN (p≥0.042), but only SpA macrophages produced increased TNF-α in response to CL097 (p=0.029). IL-23 production differed in AS and SpA macrophages: Only non-AS SpA cells produced increased IL-23 in response to all agonists as compared to control (p≥0.042). Subgroup analysis: Axial disease and sex were not significant. HLA-B27 presence was only significant in unstimulated SpA IL-23 (p=0.006). Current biologic therapy only affected AS TNF-α and IL-6 responses to PGN and LPS, respectively (p=0.016). Response patterns: No one patient produced the maximum amount of every cytokine analyzed. Also, different patients were maximal producers for individual agonists. Groups of 2-5 subjects displayed nearly identical patterns of response to the different agonists. For example, paired subjects showed a correlation in IL-23 production R≥0.92 (p≤0.028).
Conclusion:
Both AS and SpA patients produced excess IL-6 and TNF-α in response to PRR agonists, but only non-AS patients produced excess IL-23 in this study. Potential issues were sample size, positive selection of monocytes, less biologic use and more female subjects compared to previous studies. Although numbers are small, the different results (e.g. effects of biologic use) in AS and non-AS SpA puts into question the extent of shared pathogenesis. Finally, the emergence of distinct patterns of PRR response may reflect shared variations at individual immunomodulatory gene loci.
Disclosure:
Y. P. Liu,
None;
A. Bomkamp,
None;
J. Eickhoff,
None;
J. Schneck,
None;
M. Khan,
None;
J. Smith,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pattern-recognition-receptor-stimulated-cytokine-expression-by-spondyloarthritis-patient-macrophages/