Disentangling patient, disease, and treatment effects: proteomic and metabolomic differences in early versus established psoriatic arthritis
Rheumatology Advances in Practice, 2025
Bentvelzen M., el Bouhaddani S., Spierings J., Vonkeman H., Mooij S., Schipper L., Herman A., Mastbergen S., Uh H., Welsing P.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology | Serum |  Olink Target 96 |
Abstract
Objectives
Psoriatic Arthritis (PsA) is a heterogeneous inflammatory disease with unclear pathobiology. Biological mechanisms may change over time with disease progression or treatment and may correlate with specific characteristics of PsA. This study aimed to identify differences in proteomic and metabolomic profiles between disease-modifying anti-rheumatic drugs naïve (DN) and DMARD-failing (DF) PsA patients.
Methods
In the TOFA-PREDICT trial discovery cohort, baseline data from 40 DN and 40 DF PsA patients with active disease (all fulfilling the Classification Criteria for Psoriatic Arthritis) were analysed. The aim was to identify (1) differences in proteomic and metabolomic profiles using univariate (Welch’s t-test) and multivariate (XGBoost, and sPLS-DA) approaches, (2) potential mediation of these differences by patient, disease and treatment characteristics, and (3) biological functions of identified markers through enrichment analysis.
Results
36 proteins and 25 metabolites differentiated DN from DF PsA patients. Mediation analysis indicated that most differences are independent of clinical characteristics or current use of medication. Eleven proteins and two metabolites were (partially) mediated by psoriasis area and severity index (PASI), C-reactive protein level, erythrocyte sedimentation rate, tender joint count-68, disease duration, or smoking. Enrichment analysis highlighted an over-representation of immune and inflammatory proteins, while metabolomic markers were predominantly glycerophospholipids, with no significant pathway enrichment.
Conclusion
This study reveals distinct proteomic and metabolomic profiles between DN and DF PsA patients and highlights markers potentially involved in PsA pathogenesis. These findings emphasise the biological heterogeneity of PsA patients and the need to consider the disease phase in proteomic and metabolomic analysis.
Trial registration number
www.clinicaltrialsregister.eu/; 2017-003900-28.