1306 Neuropsychiatric manifestations in childhood-onset systemic lupus erythematosus: association with N-Methyl-D- aspartate receptor NR2 subunit and cytokines

Background Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease, which causes systemic involvement, including within the central nervous system (CNS). Since biomarkers for neuropsychiatric manifestations (NPM) are still an incognita, the aim of this study was to assess whether serum levels of the NR-2 subunit of the N-methyl-D-aspartate glutamate receptor and cytokines were associated with NPM in patients with cSLE. Methods Patients diagnosed with cSLE were included at this cross-sectional study. NPM were evaluated according to the American College of Rheumatology (ACR) classification. Assessment of cognitive impairment was performed using Automated Neuropsychological Assessment Metrics (ANAM) and Montreal Cognitive Assessment (MoCA). Anxiety and depression symptoms were assessed using the Beck Anxiety Inventory (BAI) and Beck's Depression Inventory (BDI), respectively. Serum levels of NR-2 were evaluated by ELISA, while serum levels of IL-4, IL-6, IL-10, IL-12, TNF and IFN-γ were measured by Luminex. Results 155 patients were included, divided into three groups: recent NPM (with NPM at the blood collection), previous NPM (without NPM during the time of blood collection, however with previous NPM) and absent NPM (without the presence of NPM at any time since the diagnosis of cSLE). The most observed NPM were anxiety (70.9%), depression (47.3%), cognitive impairment (30.9%) and headache (5.5%). Serum NR-2 levels did not differ between groups. Serum concentrations of IL-10 (11.2 x 7.0pg/ml, p= 0.040), IL-12 (3.5 x 2.0pg/ml, p=0.002,), IFN-γ (12.2 x 8.9 pg/mL, p=0.003) and TNF (8.8 x 6.2 pg/mL, p=0.029) were higher in the recent MNP group when compared to the absent MNP group. Furthermore, higher serum concentrations of IL-12 were observed in patients with anxiety (3.5 x 2.9pg/mL, p=0.035), IL-4 (36.0 x 70.8pg/mL, p=0.036) and IL-6 (1.7 x 4.4pg/mL, p=0.019) in patients without cognitive impairment and NR-2 in patients with depression (9.9 x 8.5ng/mL, p=0.032). Patients with cognitive disorders had lower percentages of correct answers in the ANAM subtests, in addition to the highest score in the performance validity index, characteristic of the cognitive disorder (p<0.001). Conclusion Th1 serum cytokines were associated to cSLE patients with CNS involvement. Furthermore, IL-12 and NR-2 can be considered possible serum biomarkers for anxiety and depression in cSLE.