Serum metabolomic profiling identifies potential biomarkers in arthritis in older adults: an exploratory study

Seronegative elderly-onset rheumatoid arthritis (EORA)^neg and polymyalgia rheumatica (PMR) have similar clinical characteristics making them difficult to distinguish based on clinical features. We hypothesized that the study of serum metabolome could identify potential biomarkers of PMR vs. EORA^neg.

Arthritis in older adults (ARTIEL) is an observational prospective cohort with patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples were compared at baseline with 18 controls. A thorough clinical examination was conducted. A Bruker Avance 600 MHz spectrometer was used to acquire Nuclear Magnetic Resonance (NMR) spectra of serum samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification.Student t-test, one-way ANOVA, binary linear regression and ROC curve, Pearson's correlation along with pathway analyses were conducted.

Twenty-eight patients were diagnosed with EORA^neg and 20 with PMR. EORA^neg patients had a mean disease activity score (DAS)-Erythrocyte Sedimentation Rate (ESR) of 6.21 ± 1.00. All PMR patients reported shoulder pain, and 90% reported pelvic pain. Fifty-eight polar metabolites were identified. Of these, 3-hydroxybutyrate, acetate, glucose, glycine, lactate, and o-acetylcholine (o-ACh), were significantly different between groups. Of interest, IL-6 correlated with different metabolites in PMR and EORA^neg suggesting different inflammatory activated pathways. Finally, lactate, o-ACh, taurine, and sex (female) were identified as distinguishable factors of PMR from EORA^neg with a sensitivity of 90%, specificity of 92.3%, and an AUC of 0.925 (p < 0.001).

These results suggest that EORA^neg and PMR have different serum metabolomic profiles that might be related to their pathobiology and can be used as biomarker to discriminate between both diseases.