Date: Monday, November 9, 2020
Session Type: Abstract Session
Session Time: 11:00AM-11:50AM
Background/Purpose: To analyze 1H-MRS brain metabolites in a longitudinal study and to determine clinical, laboratory and treatment features associated with its occurrence. To determine, additionally if sera Th1 (IL-12, TNF-α, IFN-γ), Th2 (IL-6 and IL-10), Th17 (IL-17) cytokines levels, neurofilament (NF-H) and S100β influence brain metabolite levels.
Methods: We included 123 consecutive cSLE patients [median age 16 years (range 7-31)] from the Pediatric Rheumatology outpatient unit and 76 healthy controls (HC) [median age 18 years (8-33)]. All patients underwent two magnetic resonance imaging (MRI) exams during a period of 13.5 ± 9.4 months. 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), glutamate (Glu), glutamine (Gln) 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 drug exposures. Th1 (IL-12, TNF-α, IFN-γ), Th2 (IL-6 and IL-10), Th17 (IL-17) cytokines levels, S100β and NF-H levels were measured by ELISA using commercial kits. Data were compared by non-parametric tests.
Results: NAA/Cr ratio (p=0.021) and Lac/Cr ratio (p=0.009) levels were significantly decreased and Glu/Cr ratio (0.004) and Gln/Cr ratio levels (p=0.042) were increased in cSLE patients when compared to HC. During follow-up time, no significant fluctuation in metabolites was observed in both groups. We observed that persistent reduction of NAA/Cr ratio was associated with neuropsychiatric manifestations [symptoms of anxiety (p=0.04), symptoms of depression (p=0.006)], presence of autoantibodies [antiphospholipid antibodies (p=0.03)] and cytokine levels [TNF-α (r=-0.546; p=0.0023) and INF γ (r=-0.746; p=0.0002)]. Persistent increased Cho/Cr ratio was associated with cognitive dysfunction (0.003), anti-SM (0.005), and correlated with S100β (r=0.641; p=0.005) and NF-H (r=-0.225, p=0.05). Increased Glu/Cr ratio was associated with stroke (0.043) and symptoms of depression (p= 0.0007).
Conclusion: We observed significant persistent axonal dysfunction in cSLE associated with increased inflammatory markers, autoantibodies and neuropsychiatric manifestations. Persistent axonal dysfunction could be a marker of future structural damage and patients should be followed-up closely.
To cite this abstract in AMA style:Frittoli R, Rodrigues D, Lapa A, Postal M, Marini R, Castellano G, Cendes F, Rittner L, Appenzeller S. Longitudinal Evaluation of Axonal Dysfunction, Neuronal Markers and Serum Cytokines in Childhood-onset Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/longitudinal-evaluation-of-axonal-dysfunction-neuronal-markers-and-serum-cytokines-in-childhood-onset-systemic-lupus-erythematosus/. Accessed November 29, 2021.
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