Raman spectroscopy as a promising diagnostic method for rheumatoid arthritis.

: Diagnosis of rheumatoid arthritis (RA) basically relies on clinical symptoms and autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF). However, the lack of autoantibodies is still a dilemma clinically in seronegative RA, especially in the early stage of the disease. This study aimed to provide a unique disease fingerprint with high diagnostic value to discriminate RA based on Raman spectroscopy. : Raman spectroscopy provides a repertoire of biomolecules in serum from RA. Multivariate dimension-reducing methods and machine-learning algorithms were exploited to reveal the intrinsic differences and the potential discrimination power. The underlying differential biomolecules were retrieved by the assignment of Raman peaks. Moreover, the correlations between the spectral differences and RA patient's clinical and immunological manifestations were also analyzed. : RA patients exhibited unique Raman spectra characterized by biomolecular alterations during the disease progression. The discrimination power yielded 97.3% sensitivity and 94.8% specificity for RA diagnosis. In the recognition of ACPA-negative RA, the sensitivity and specificity also reached 95.6% and 92.8%, respectively. In particular, the differential Raman spectrum peaks of RA patients mainly represented lipids, amino acids, glycogen, and fatty acids. Further analysis showed that the different serum Raman spectra correlated with the clinical features of RA, including disease duration, RF, anticyclic citrullinated peptide antibodies (anti-CCPs), IgA, IgM, IgG, tender joint count, and swollen joint count (|rs| = 0.15-0.52, < 0.05). : Raman spectroscopy was revealed to be a promising diagnostic method for RA, especially for ACPA-negative patients.