A severely affected MRL/Lpr mouse exhibits a divergent clinical–immune profile associated with profound metabolic alteration
Abstract
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.
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BibTeX
@article{matmat2026severely,
title = {{A severely affected MRL/Lpr mouse exhibits a divergent clinical–immune profile associated with profound metabolic alteration}},
author = {Karim Matmat and Carole Jamey and Noémie Karabacz and Daniel Brumaru and Jérôme de Seze and Ayikoé-Guy Mensah-Nyagan and Hélène Jeltsch-David},
journal = {Immunology Letters},
year = {2026},
month = sep,
doi = {10.1016/j.imlet.2026.107242},
url = {https://hal.science/hal-05765499v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A severely affected MRL/Lpr mouse exhibits a divergent clinical–immune profile associated with profound metabolic alteration
AU - Karim Matmat
AU - Carole Jamey
AU - Noémie Karabacz
AU - Daniel Brumaru
AU - Jérôme de Seze
AU - Ayikoé-Guy Mensah-Nyagan
AU - Hélène Jeltsch-David
PY - 2026
DA - 2026/09/25
JO - Immunology Letters
DO - 10.1016/j.imlet.2026.107242
UR - https://hal.science/hal-05765499v1
AB - 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.
SN - 0165-2478
ER -