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Abstract
Purpose Cognitive dysfunction (CD) and mood disorders (MD) are among the most frequent neuropsychiatric (NP) events in Systemic Lupus Erythematosus (SLE), but their pathogenesis has not been fully clarified yet. A potential role of antineuronal antibodies in NP-SLE patients is currently being investigated. The primary aim of the study was to explore the effects of anti-ribosomal-P (anti-Rib-P) and anti-DWEYS antibodies on CDs and MDs and their relationship with functional Magnetic Resonance Imaging (MRI) brain connectivity in patients affected by SLE.
Methods A cross-sectional study was conducted between April 2019 and February 2020, including consecutive adult patients who fulfilled the ACR/EULAR 2019 SLE criteria.
Demographics, serological, ongoing medications, SLEDAI and SLICC/Damage Index (SDI) were recorded. Serum level quantification for anti-Rib-P and anti-DWEYS antibodies were performed using an ELISA. A battery of neuropsychological testing exploring cognitive domains, depression and quality of life was interpreted by a neuropsychologist. A resting-state functional connectivity (rs-fc) MRI analysis was performed within 2 weeks since the neuropsychological status assessments. Two region of interest to region of interest (ROI-to-ROI) analyses with the graph theory was performed.
Results Thirty-three SLE patients (9% male) were enrolled, mean age 43.5 (+-14) years, and median disease duration of 10.4 years (IQR 2.9–25.4). The daily median prednisone (PDN) dose was 6.4 mg (3.8–13.5). Anti-Rib-P were positive (range 0–255 U/ml) in 6 patients (18.2%) and anti-DWEYS (range 0–1.8 OD) in 14 (42.4%).
Nineteen out of 33 patients (57.6%) showed at least a cognitive test alteration. The most frequent cognitive deficits were memory disturbances, found in 6.1–27.3% of the population evaluated, according to the cognitive test used, followed by alterations in executive functions (12.1–21.9%), psychomotor speed (18.2%) and attention (3–12.1%), but no significant association with antibodies was found. Depression was found in 14 (42.4%) patients using the Center for Epidemiologic Studies Depression Scale (CES-D) as a screening instrument. In multiple regression backward models, after correction for age, disease duration, SLEDAI and SDI, the CES-D showed an independent association with anti-Rib-P titer (β=0.32 per U/ml; p=0.049) and PDN daily dose (β=0.38 per mg/day; p=0.023). The rs-fc MRI analysis revealed a statistically significant association between the titer of anti-Rib-P and many altered properties of the brain ROIs (Figure 1), but no effects of PDN daily dose on specific cerebral networks.
Results of rs-fc MR Analysis 1 (effects of Anti-rib-P titer) on cerebral networks. The regions with decreased or increased properties are shown in blue and red nodes, respectively (p<0.01). The node size represents the significance of the between-group differences in the nodal degree
Conclusions Anti-Rib-P antibodies and PDN daily dose are associated with depressive symptoms. Anti-Rib-P antibodies are also associated with changes in brain network properties in SLE patients, which add knowledge to their pathogenetic effect.
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