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.

Abstract

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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