A severely affected MRL/Lpr mouse exhibits a divergent clinical-immune profile associated with profound metabolic alteration.

Systemic lupus erythematosus (SLE) exhibits marked clinical and biological heterogeneity that is poorly captured by group-based analyses. Using the MRL/Lpr model, we describe an individual mouse displaying a severe phenotype, and provide a characterization combining clinical assessment, inflammatory profiling, neuroaxonal injury, and targeted metabolomics. Despite severe disease, this animal did not display a globally exaggerated cytokine profile relative to other MRL/Lpr mice, although TNFα and IL-1β ranked among the highest in the cohort. In contrast, plasma neurofilament light chain (NfL) was markedly elevated, and metabolomic profiling revealed pronounced disruptions in urea-cycle intermediates, sulfur amino-acid metabolism and muscle-derived metabolites, together with a broad depletion of circulating amino acids. These observations raise the possibility that, at advanced disease stages, circulating cytokine levels may plateau and lose discriminative capacity, whereas metabolic readouts may retain greater capacity to track disease severity.