Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway

Objective: Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).

Methods: This was a cross-sectional pilot study comparing metabolomic sera and skin profiles of patients with CLE and normal controls. Patients were recruited from outpatient dermatology clinics at the University of Texas Southwestern and Parkland Health in Dallas, Texas, from January 2019 to October 2020. Skin and serum samples underwent LC-MS analysis. Disease sample metabolite levels were compared with controls, with significance levels adjusted for multiple hypothesis testing.

Results: 17 serum samples (9 CLE, 8 control) and 11 skin samples (5 CLE, 6 control) were analysed using LC-MS, yielding 313 known unique metabolic structures from CLE samples. Patients with CLE were found to have 11 metabolites of differential abundance in the skin, but only 2 in the sera. CLE skin showed increased levels of citrulline (log₂ fold change (FC)=1.15, p=0.02) and uracil (log₂FC=1.79, p=0.04), and downregulation of cyclic ADP ribose (cADPr) (log₂FC=0.83, p=0.04), nicotinamide mononucleotide (NMN) (log₂FC=0.75, p=0.016) and nicotinamide adenine dinucleotide (NAD⁺) (log₂FC=0.86, p=0.016) versus control skin. CLE sera had increased arabinose (log₂FC=1.17, p=0.02) and cystine (log₂FC=1.04, p=0.03) compared with control sera.

Conclusions: Metabolites associated with the NAD⁺ pathway may be dysregulated in the skin of patients with CLE. Available treatments including nicotinamide supplementation and anti-CD38 biologics that can correct these abnormalities can be further investigated in patients with CLE.