Background/Purpose: Chronic inflammation is closely associated with an increased risk of cardiovascular diseases (CVD) through the activation of the immune system and the release of inflammatory molecules like C-reactive protein (CRP). In Spondyloarthritis (SpA), prolonged inflammation can harm the vascular system, further raising the likelihood of developing CVD. Currently, there is a lack of tools available to identify patients who had persistent inflammation and its connection to CVD. The aim of this study was to analyze the clinical and molecular characteristics associated with persistent inflammation and to identify potential plasma protein biomarkers for an easy identification of patients with prolonged inflammation over the years in SpA patients

Methods: A study involving 136 patients diagnosed with SpA was conducted. Clinical and laboratory parameters, as well as CVD risk factors were recorded. To assess the presence of persistent inflammation, levels of CRP were retrospectively collected for a period of 5 years. A patient was classified as having persistent inflammation if increased CRP levels were detected in at 100% of the measurements taken during the preceding 5-year timeframe. Radiographs of the cervical spine, lumbar spine, and sacroiliac joints were obtained. Lateral views of the cervical and lumbar spine were scored according to the mSASSS index. Sacroiliitis was scored from right side and left side pelvic radiographs using the modified New York criteria. The plasma levels of 92 proteins related to CVD were analyzed using proximity extension assay (PEA) technology (Olink Target 96 CVD III panel, Cobiomic Biosciences).

Results: 36% of SpA patients had persistence of inflammation. Clinically, these patients showed higher levels of disease activity (ASDAS), peripheral forms, structural damage (mSASSS), acute phase reactants, altered metabolic profile, activation of complement component and higher rates of cardiometabolic comorbidities compared to non-persistent SpA patients. At molecular level, 16 CVD-related plasma proteins were significantly associated with presence of persistence of inflammation: MMP-9, RETN, PGLYRP-1, UPAR, PRTN-3, TR, RARRES-2, AZU-1, GP-6, TNF-R1, MPO, GDF-15, CCL-16, IL-2RA, PI3 and PDGF. The most contributing proteins to differentiate groups of SpA patients with persistent and non-persistent inflammation were MMP-9, RETN, PGLYRP-1 and UPAR. The combination of these proteins could predict the presence of constant persistent inflammation with an AUC=0.865. These proteins exhibit specific biological functions such as neutrophil degranulation, immune response, leukocyte migration and apoptosis.

Conclusion: 1) persistent inflammation over five years was associated with peripheral forms, increased disease activity and radiographical damage in SpA patients. 2) SpA patients with persistent inflammation display a pronounced alteration in their plasma CVD protein profile, indicating a connection between subclinical CVD risk and chronic inflammation. 3) we identified novel biomarkers that have the potential to differentiate SpA patients with persistent inflammation, offering valuable insights for therapeutic approaches.
Funded by ISCIII (PMP21/00119).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-and-molecular-patterns-associated-with-persistence-of-inflammation-in-spondyloarthritis-patients-unveiling-potential-biomarkers/