Background/Purpose: Involvement of the central nervous system is frequently observed in childhood-onset SLE patients (cSLE). Proton magnetic spectroscopy (1H-MRS) is an important non-invasive method of quantification of biological metabolites. Abnormalities in brain metabolites may predict future damage, such as lesions and atrophy in adults-onset SLE, however 1H-MRS have never been evaluated in cSLE. Objective: To determine the presence of axonal dysfunction in cSLE and to determine clinical, laboratory and treatment features associated with its occurrence. To associate axonal dysfunction with sera Th1 (IL-12, TNF-α, IFN-γ), Th2 (IL-6 and IL-10), Th17 (IL-17) cytokines levels and antiribosomal P protein antibodies (anti-P) and S100β. 

Methods: We included 77 consecutive cSLE patients [median age 16 years (range 7-31)] from the Rheumatology outpatient unit (State University of Campinas) and 66 healthy controls [median age 18 years (8-32)]. We performed multi voxel 1H-MRS using point resolved spectroscopy sequence over the superior–posterior region of the corpus callosum (3T Phillips^®scanner) and signals from N-acetylaspartate compounds (NAA), choline-based compounds (Cho); creatine containing compounds (Cr) and lactate (Lac) were measured and metabolites/Cr ratios were determined. A complete clinical, laboratory and neurological evaluation was performed in all subjects. Neurological manifestations were analyzed according to the ACR classification criteria. Mood and anxiety disorders were determined through Beck Depression and Beck Anxiety Inventory. SLE patients were further assessed for clinical and laboratory SLE manifestations, disease activity [SLE Disease Activity Index (SLEDAI)], damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] and current and cumulative drug exposures. Th1 (IL-12, TNF-α, IFN-γ), Th2 (IL-6 and IL-10), Th17 (IL-17) cytokines levels, S100β levels and anti-P were measured by ELISA using commercial kits. Data were compared by non-parametric tests. 

Results: NAA/Cr ratio (p=0.017) and Lac/Cr ratio (p=0.014) levels were significantly decreased and Cho/Cr ratio levels (p=0.038) were increased in cSLE patients when compared to healthy controls. We observed that Cho/Cr ratio was associated with symptoms of anxiety (p=0.02), cognitive decline (p=0.03), corticosteroid use (p=0.034) and correlated with IL-6 (r=0.568; p=0.002). NAA/Cr ratio was associated with disease activity (p=0.01) and correlated with IL-4 (r=0.375; p=0.024). Lac/Cr ratio was associated with symptoms of depression (p=0.016), presence of anti-P (p=0.04) and correlated with IFN-γ (r=0.611; p=0.004). 

Conclusion: We observed significant axonal dysfunction in cSLE. Decreased NAA/Cr ratio was associated with disease activity and sera IL-4 levels and increased Cho/Cr ratio was associated with neuropsychiatric manifestations, cumulative dose of corticosteroids and IL-6, suggesting brain injury. Lac/Cr was associated with symptoms of depression, anti-P and IFN-γ. NAA, Cho and Lac may be useful as biomarkers in neuropsychiatric cSLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/axonal-dysfunction-in-childhood-onset-systemic-lupus-erythematosus-association-with-neuropsychiatric-manifestations-and-disease-activity/