P0158 Immune profiles of Inflammatory Bowel Disease and Spondyloarthritis call for personalized medicine
Authors: Veltkamp S , van Gaalen F A , Samsom J N , van der Meulen-de Jong A E , Voorneveld P W 
Published: January 2025

Background

Inflammatory bowel disease (IBD) is strongly associated with joint inflammation, as is highlighted by the high prevalence of spondyloarthritis (SpA) in patients with IBD (up to 13%) compared to the general population (0.2-1.6%) [1, 2]. IBD and SpA have many overlapping features, including genetic risk factors and therapies targeting TNF-α, IL-23, or JAK. However, therapies for both diseases fail to break the cycle of chronic inflammation. Disease heterogeneity likely plays a role in this, underscoring the need to improve management and refine classification.

Methods

In this study, 92 inflammation-related proteins were quantified in serum of patients from an IBD and a SpA cohort using a proximity extension assay. False discovery rates (FDR) &lt;0.05 were considered significant. The IBD cohort included 255 IBD patients with (n=155) and without (n=100) self-reported joint complaints [3]. From the patients with joint complaints, 15 had a SpA diagnosis. The SpA cohort included 169 patients with chronic back pain (CBP) (≥3 months, ≤2 years) of unknown origin [4]. After 2 years of follow-up, 85 patients had proven axial SpA (axSpA). Serum samples were taken at baseline, and 151 samples from the SpA cohort and 241 samples from the IBD cohort passed quality control and were included for analysis.

Results

Twenty proteins were differentially expressed between 95 IBD patients without joint complaints and 79 proven axSpA patients; 12 were higher in IBD patients (including 4EBP1, FGF21, CD8A, CCL20, and CCL19), and 8 were higher in axSpA patients (including CASP8, ST1A1, FGF19, ENRAGE, and SIRT2) (Fig. 1). Hierarchical clustering revealed that patients clustered according to their diagnosis. However, comparison of IBD patients with joint complaints with and without SpA showed that their serum immune profiles are fairly consistent, with only 3 differentially expressed proteins (Fig. 2). In addition, comparison of CBP (back joint complaints) patients with and without SpA showed no differentially expressed proteins. Hierarchical clustering of these patient groups revealed that among patients with joint complaints, those with a SpA diagnosis did not cluster together.

Conclusion

IBD patients without joint complaints and axSpA patients without IBD have distinct serum immune profiles. Within IBD patients with joint complaints and in patients with chronic back pain, the serum immune profile is fairly consistent, regardless of SpA diagnosis. This result emphasizes the need to refine disease classification and shift from diagnosis-based treatment to a more personalized approach. The inflammation signatures of patients with chronic inflammatory diseases should be further investigated to provide insights for enhancing disease management.

References

1.Karreman, M.C., et al., The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis. J Crohns Colitis, 2017. 11(5): p. 631-642.

2.Stolwijk, C., et al., Global Prevalence of Spondyloarthritis: A Systematic Review and Meta-Regression Analysis. Arthritis Care Res (Hoboken), 2016. 68(9): p. 1320-31.

3.van Erp, S.J., et al., Classifying Back Pain and Peripheral Joint Complaints in Inflammatory Bowel Disease Patients: A Prospective Longitudinal Follow-up Study. J Crohns Colitis, 2016. 10(2): p. 166-75.

4.Marques, M.L., et al., Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort. Ann Rheum Dis, 2024. 83(5): p. 589-598.