The differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is very difficult because of the similarity of symptoms and the inaccessibility of reliable clinical markers. Chronic inflammation can cause major changes in the serum metabolome and lipidome. Hence, differences in serum metabolites and lipids that could assist in improving the differential diagnosis of these diseases were tested.

Sera from negRA and PsA patients with confirmed diagnosis were collected to form a biomarker-discovery and a blinded validation cohort. Samples were analyzed using proton nuclear magnetic resonance. Metabolite concentrations were considered from the spectra and used to select the variables in building a multivariate diagnostic model.

Univariate analysis revealed the differences in serological concentrations of amino acids such as alanine, threonine, phenylalanine, leucine and valine along with organic compounds such as creatine, acetate, lactate and choline. The analysis also showed differences in the lipid ratios L3/L1, L5/L1 and L6/L1; however, it yielded area under the curve (AUC) values lower than 70% that indicates poor specificity and sensitivity.

A multivariate diagnostic model comprised of age, gender, and the concentrations of alanine, succinate, creatine, phosphate and the lipid ratios L2/L1, L5/L1 and L6/L1. This diagnostic model improved the specificity and sensitivity of the diagnosis with an AUC of 84.5%. By using the biomarker model, 71% of patients from a blinded validation cohort were appropriately categorized.

The study concluded that PsA and negRA have distinct serum metabolomic and lipidomic signatures which can be used as biomarkers to differentiate between them. This diagnostic model might become a valuable tool for a confirmed diagnosis of negRA or PsA patients after validation in larger multiethnic cohorts.

Source: Souto-Carneiro M, Tóth L, Behnisch R, et al. Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis. Ann Rheum Dis. 2020;79(4):499-506. doi:10.1136/annrheumdis-2019-216374