Serum Metabolic Fingerprints Characterize Systemic Lupus Erythematosus

Metabolic fingerprints in serum characterize diverse diseases for diagnostics and biomarker discovery. The identification of systemic lupus erythematosus (SLE) by serum metabolic fingerprints (SMFs) will facilitate precision medicine in SLE in an early and designed manner. Here, a discovery cohort of 731 individuals including 357 SLE patients and 374 healthy controls (HCs), and a validation cohort of 184 individuals (SLE/HC, 91/93) are constructed. Each SMF is directly recorded by nano‐assisted laser desorption/ionization mass spectrometry (LDI MS) within 1 minute using 1 µL of native serum, which contains 908 mass to charge features. Sparse learning of SMFs achieves the SLE identification with sensitivity/specificity and area‐under‐the‐curve (AUC) up to 86.0%/92.0% and 0.950 for the discovery cohort. For the independent validation cohort, it exhibits no performance loss by affording the sensitivity/specificity and AUC of 89.0%/100.0% and 0.992. Notably, a metabolic biomarker panel is screened out from the SMFs, demonstrating the unique metabolic pattern of SLE patients different from both HCs and rheumatoid arthritis patients. In conclusion, SMFs characterize SLE by revealing its unique metabolic pattern. Different regulation of small molecule metabolites contributes to the precise diagnosis of autoimmune disease and further exploration of the pathogenic mechanisms. Systemic lupus erythematosus (SLE) with the highest area under the curve value of 0.992 by sparse learning of serum metabolic fingerprints of a large cohort of 915 individuals are characterized. A high‐performance nano‐assisted laser desorption/ionization mass spectrometry is developed for the acquisition of serum metabolic fingerprints within 1 min using 1 µL of each native serum. This work provides a promising assay for SLE precision diagnosis with high throughput and low sample consumption in clinics.