Growing evidence suggests that serotonin is an important mediator in the cross-talk between immune and bone cells, playing a role in the pathogenesis of various types of inflammatory arthritis (IA). However, the relationship between circulating serotonin and different outcomes in three most prevalent IA - rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA), remains limited and requires further investigation. This study was performed to evaluate variations in serotonin serum levels among RA, PsA, and axSpA and to explore the utility of this biochemical marker in the assessment of disease activity and health status measurements provided by the Multi-Dimensional Health Assessment Questionnaire (MDHAQ). This was a cross-sectional study using data from the PolNorRHEUMA registry. Demographic and clinical data, as well as blood samples, were collected during routine visits to the rheumatology outpatient clinic. We included 60 patients (20 with RA, 20 with PsA, and 20 with axSpA) and 45 healthy controls, with a mean age of 49 years and 56.2% female. A reliable liquid chromatography–tandem mass spectrometry (LC-MS) method was used for the quantitative determination of serotonin in blood serum. Analysis of serotonin levels, based on 105 observations and adjusted for age, SSRI/SNRI intake and physical activity, revealed a significant elevation in the patient groups compared with the controls (p < 0.001): 134.00 ng/mL in healthy controls vs. 176.00 ng/mL in RA, 183 ng/mL in PsA, and 184.00 ng/mL in axSpA, with no statistically significant differences between the respective forms of IA. We found no significant correlation between the serotonin concentration and disease activity composite scores. A sample of 51 patients revealed a significant positive correlation between the serotonin concentration and global MDHAQ scores (β = 0.01, p = 0.009), indicating that an increase in serotonin levels is associated with worsening patient-reported health status. The serotonin serum concentration was higher in patients with RA, PsA, and axSpA than in controls, indicating its potential as a biomarker of inflammation and worse health status. The LC-MS method was successfully applied for the analysis of serum.
