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Published on: April 24, 2020
Absence of a classically activated macrophage cytokine signature in peripheral spondylarthritis, including psoriatic
Bernard Vandooren1, Troy Noordenbos, Carmen Ambarus
1Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Objective:
Peripheral spondylarthritis (SpA) is characterized by macrophages that express CD163, a marker of alternative activation (M2). The purpose of this study was to assess whether this differential infiltration with macrophage subsets was associated with a different local inflammatory milieu in SpA as compared with rheumatoid arthritis (RA).
Methods:
The effect of SpA and RA synovial fluid (SF) on macrophage polarization was tested in vitro on normal peripheral blood monocytes. SF levels of classically activated macrophage (M1)-derived and alternatively activated macrophage (M2)-derived mediators were analyzed by enzyme-linked immunosorbent assay and multiparameter Luminex bead assay in 47 patients with non-psoriatic SpA, 55 with RA, and 15 with psoriatic arthritis (PsA). Paired synovial biopsy samples were analyzed histologically.
Results:
SF from SpA patients promoted preferential expression of the M2 markers CD163 and CD200R in vitro, even if SF levels of the prototypical M2-polarizing factors (interleukin-4 [IL-4], IL-13, and IL-10) were not increased as compared with those in RA SF. Despite a similar degree of overall joint inflammation in SpA and RA, SpA synovitis displayed strongly reduced SF levels of M1-derived, but not M2-derived, mediators, such as tumor necrosis factor alpha (TNFalpha), IL-1beta, IL-12p70, and interferon-gamma-inducible protein 10. SF levels of M1-derived mediators correlated well with peripheral joint inflammation in RA, but neither these mediators nor IL-1alpha and IL-17 did so in SpA. Of interest, the SF cytokine profile in PsA, a more destructive subtype of SpA, was similar to that in non-psoriatic SpA.
Conclusion:
The local inflammatory milieu is clearly different in SpA as compared with RA peripheral arthritis. Synovitis in SpA, including that in PsA, is characterized by a selective decrease in M1-derived proinflammatory mediators, such as TNFalpha and IL-1beta.
Insights
Peripheral spondylarthritis (SpA) involves M2 macrophages, unlike rheumatoid arthritis (RA). SpA synovitis shows reduced M1 mediators, indicating a distinct inflammatory environment in SpA joints compared to RA.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Peripheral spondylarthritis (SpA) is associated with CD163-expressing M2 macrophages.
- Understanding the local inflammatory environment in SpA is crucial for differentiating it from rheumatoid arthritis (RA).
Purpose of the Study:
- To investigate the local inflammatory milieu in SpA compared to RA.
- To determine if macrophage subset infiltration correlates with distinct inflammatory mediators in SpA synovitis.
Main Methods:
- Monocytes were cultured in vitro with synovial fluid (SF) from SpA and RA patients to assess macrophage polarization.
- SF and synovial biopsy samples from patients with SpA, RA, and psoriatic arthritis (PsA) were analyzed for M1 and M2 mediator levels.
- Enzyme-linked immunosorbent assay and Luminex assays were used to quantify cytokine levels.
Main Results:
- SpA SF promoted M2 marker expression in vitro, despite similar M2-polarizing factor levels as RA SF.
- SpA synovitis exhibited significantly lower levels of M1 mediators (e.g., TNF-alpha, IL-1beta) compared to RA.
- M1 mediator levels correlated with joint inflammation in RA but not in SpA; PsA showed a similar cytokine profile to non-psoriatic SpA.
Conclusions:
- The local inflammatory milieu in peripheral SpA differs significantly from RA.
- SpA synovitis is characterized by a selective reduction in M1-derived pro-inflammatory mediators.
- These findings highlight distinct inflammatory pathways in SpA, including PsA.
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