The Evolving Landscape of Axial Spondyloarthritis

The IL-23 axis in axSpA represents a cornerstone of disease pathogenesis. However, clinical trials targeting this pathway have yielded inconsistent results across different disease subtypes. Researchers recently investigated how cytokine levels and regulatory cell populations shift as patients progress from non-radiographic axial spondyloarthritis (nr-axSpA) to radiographic axial spondyloarthritis (r-axSpA). Their findings suggest that the immune environment changes significantly between these disease stages.

Early Activity of the IL-23 axis in axSpA

Evidence shows that interleukin-23 (IL-23) activity is significantly higher during the early, non-radiographic stage of the disease. Specifically, patients with nr-axSpA exhibit higher serum IL-23 levels compared to those with radiographic changes. Furthermore, peripheral dendritic cells in the early stage produce more IL-23. In contrast, interleukin-17A levels remain comparable between both groups. Consequently, these findings highlight a potentially greater role for IL-23 in the initiation phase of axial spondyloarthritis. Moreover, monocyte-derived dendritic cells from early-stage patients stimulate stronger pro-inflammatory responses in healthy T cells.

The Shift Toward Regulatory Tr1 Cells

As the disease progresses toward the radiographic stage, the body appears to mount a stronger regulatory response. Notably, patients with r-axSpA demonstrate higher proportions of type 1 regulatory T (Tr1) cells. These cells produce interleukin-10 (IL-10), which serves as a crucial anti-inflammatory mediator. Therefore, the lower levels of Tr1 cells found in non-radiographic patients might contribute to the heightened inflammation seen early on. Interestingly, IL-10 treatment effectively reduces IL-23 production in cells from early-stage patients but has little effect in the later stages. This suggests that regulatory mechanisms become more robust as the condition stabilizes or progresses to bone formation.

Clinical Implications for Rheumatologists

Understanding these stage-specific dynamics is essential for optimizing treatment strategies in India. Specifically, the high activity of the IL-23 axis in axSpA during the non-radiographic phase may explain why certain biological therapies show varying efficacy. Early intervention that targets this specific axis could potentially alter the disease course before permanent radiographic damage occurs. Additionally, clinicians should consider the evolving role of IL-10 and regulatory T cells when monitoring disease activity and long-term prognosis.

Frequently Asked Questions

How does IL-23 production differ between nr-axSpA and r-axSpA?

Patients with non-radiographic axial spondyloarthritis (nr-axSpA) typically have higher serum IL-23 levels and higher production from dendritic cells than those with radiographic disease.

What role do Tr1 cells play in axial spondyloarthritis?

Tr1 cells are regulatory cells that produce the anti-inflammatory cytokine IL-10. Their levels are lower in early disease stages but increase as the condition progresses to the radiographic stage.

Why does IL-23 inhibition work differently across stages?

The IL-23 axis is most active in the early stages of axial spondyloarthritis. Consequently, targeting this pathway might be more effective before the immune profile shifts and regulatory mechanisms like Tr1 cells become more prominent.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional relationship. Refer to the latest local and national guidelines for clinical practice.

References

Yeo J et al. Dynamics of interleukin-23/interleukin-17 axis and type 1 regulatory T cells across disease stages in axial spondyloarthritis. Clin Exp Rheumatol. 2026 Feb 27. doi: 10.55563/clinexprheumatol/ijkhjz. PMID: 41758549.