Axonal dysfunction is associated with interferon-γ levels in childhood-onset systemic lupus erythematosus: a multivoxel magnetic resonance spectroscopy study.

OBJECTIVE Axonal/neuronal damage has been shown to be a pathological finding that precedes neuropsychiatric manifestations in systemic lupus erythematosus (SLE). Therefore, the objective of this study was to determine the presence of axonal dysfunction in childhood-onset SLE patients (cSLE) and to determine clinical, immunological, and treatment features associated with its occurrence. METHODS We included 86 consecutive cSLE patients [median age 17 years (range 5-28)] and 71 controls [median age 18 years (5-28)]. We performed Proton Magnetic Resonance Spectroscopic Imaging (1H-MRSI) using point resolved spectroscopy sequence (PRESS) over the superior-posterior region of the corpus callosum and signals from N-acetylaspartate compounds (NAA), choline-based compounds (CHO); creatine containing compounds (Cr), myo-inositol (mI), lactate (Lac), glutamate (Glu), glutamine (Gln) and lactate (Lac) were measured and metabolites/Cr ratios were determined. Complete clinical, laboratory and neurological evaluations were performed in all subjects. Sera IL-4, IL-5, IL-6, IL-10, IL-12, IL-17, TNF- α, INF- γ cytokines levels, antiribosomal P protein antibodies (anti-P) and S100β were measured by enzyme-linked immunosorbent assay (ELISA) using commercial kits. Data were compared by non-parametric tests. RESULTS NAA/Cr ratios (p= 0.035) and Lac/Cr ratios (p= 0.019) levels were significantly decreased in cSLE patients when compared with controls. In multivariate analysis, interferon (IFN) gamma (γ) levels (OR = 4.1; 95% 2.01-7.9) and depressive symptoms (OR = 1.9; 95%CI = 1.1-3.2) were associated with NAA/Cr ratio. Increased Cho/Cr was associated with the presence of cognitive impairment (OR = 3.4; p< 0.001; 95%CI = 2.034-5.078). mI/Cr ratio correlated with cumulative glucocorticoids dosage (r = 0.361; p= 0.014). CONCLUSION NAA and CHO ratios may be useful as biomarkers in neuropsychiatric cSLE. Longitudinal studies are necessary to determine whether they predict structural damage.