Introduction
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, changes in the gut microbiota, and therapies targeting TNF-α , IL-23, or JAK [3]. However, current therapies for both diseases are unable to break the cycle of chronic inflammation, and still a significant proportion of patients fail to respond. Disease heterogeneity likely plays a role in this [4, 5], underscoring the necessity to improve management and refine classification.
Aims & Methods
In this study, 92 inflammation-related proteins were quantified in serum of patients from one IBD and one SpA cohort using the novel Olink proteomics proximity extension assay. Fold changes (FC) in expression with |log2FC| > 0.5 were considered meaningful, and false discovery rates (FDR) <0.05 were considered significant. The IBD cohort existed of 255 IBD patients with (n=155) and without (n=100) self-reported joint complaints [8]. From the patients with joint complaints, 58 fulfilled any of the SpA criteria. The SpA cohort, or SPACE cohort, consisted of 169 patients with chronic back pain (≥3 months, ≤2 years) of unknown origin [9]. After 2 years of follow-up, 85 patients had proven axSpA. Serum samples were taken at baseline, and 167/169 samples from the SPACE cohort and 241/255 samples from the IBD cohort passed quality control and were included in the analysis.
Results
Thirty-four proteins were differentially expressed between 95 IBD patients without joint complaints and 85 proven axial SpA (axSpA) patients from the SPACE cohort, of which 14 were higher in IBD patients (including 4E‑BP1, IFN‑γ, TNF, FGF‑21, CD8A, and CCL9), and 20 were higher in axSpA patients (including CASP‑8, SIRT2, STAMBP, FGF‑19, ST1A1, and EN‑RAGE). In addition, the immune profile of IBD patients with joint complaints differed from IBD patients without joint complaints: 4E‑BP1, CASP-8, STAMBP, SIRT2, AXIN1, and TNFSF14, were significantly upregulated in patients with joint complaints. Of note, if IBD patients without joint complaints were compared to the subgroup of 58 patients with joint complaints who met criteria for SpA, the same proteins showed significant upregulation, suggesting minimal difference between IBD patients with joint complaints who meet or who do not meet SpA criteria. Direct comparison of patients who met and who did not meet SpA criteria within the group of IBD patients with joint complaints indeed showed no noteworthy difference in serum immune profile. Within the SPACE cohort, comparison of patients with chronic back pain with and without axSpA diagnosis also showed no significant difference in serum protein expression.
Conclusion
This study shows that patients with axSpA versus patients with IBD without joint complaints have differing serum immune profiles. Within IBD patients with self-reported joint complaints and within patients with self-reported chronic back pain (from the SPACE cohort), no distinct difference in immune profile is observed, regardless of SpA diagnosis. The inflammation signatures of patients with chronic inflammatory diseases should be further investigated to provide insights for enhancing disease management in the future.
References
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6. 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.
7. 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.
Disclosure
FAG: grants from Stichting vrienden van Sole Mio and Stichting ASAS, grants and/or consulting fees from Abbvie, ASAS, BMS, Galapagos, Janssen, Lilly, Novartis, Pfizer, and UCB.
AEM: grants from Nestle, Norgine, Cablon, Galapagos, and ZonMW, ad boards/speaker fees from Tramedico, Janssen, Takeda, Galapagos, Vedanta, Ferring, AbbVie, and Dear Health.
PV: speaker fees from Takeda and Galapagos, advisory board: Takeda, Galapagos, Lilly, BMS, Janssen, and Abbvie