Serum immune profiling suggests overlap between IBD patients with joint complaints and patients with spondyloarthritis

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Background: Inflammatory bowel disease (IBD) and spondyloarthritis (SpA) are strongly associated, and joint complaints are common in patients with IBD. However, it remains unclear whether joint complaints in IBD merely reflect non-specific symptoms, or whether they are associated with systemic immune features overlapping with SpA. Methods: Using a proximity extension assay, 92 inflammation-related proteins were quantified in serum samples of patients from two cohorts: (i) IBD patients without (n = 100) and with joint complaints (n = 155; of whom 15 with SpA), and (ii) 169 patients with chronic back pain of unknown origin at the rheumatology outpatient clinic, where diagnosis of SpA was confirmed (n = 85) or rejected after 2 years of follow-up. Serum samples were collected at baseline. Results: IBD patients without joint complaints from cohort (i) and confirmed axSpA patients from cohort (ii) showed distinct serum immune profiles, with 20 differentially abundant proteins. Among IBD patients with joint complaints, formal SpA diagnosis had limited additional impact on the serum immune profile, with only three differentially abundant proteins between those with and without SpA. Similarly, among patients with chronic back pain, serum immune profiles were largely concordant irrespective of subsequent axSpA diagnosis. Importantly, IBD patients with joint complaints differed from IBD patients without joint complaints, and several proteins increased in this comparison overlapped with proteins increased in axSpA. Conclusions: Joint complaints in IBD are associated with a modest but detectable shift in the circulating immune profile, partly overlapping with axSpA-associated proteins. In contrast, formal SpA diagnosis adds limited additional serum-protein separation among patients who already have joint symptoms. These findings suggest that joint complaints in IBD may mark a biologically relevant subgroup beyond current SpA classification, and support longitudinal studies to determine whether this subgroup has distinct clinical trajectories or treatment responses.

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