Effect of anti-P ribosomal and anti-NR2 antibodies on depression and cognitive processes in SLE: an integrated clinical and functional MRI study

Abstract

Objectives: To explore the effects of anti-ribosomal P protein (anti-P) and anti-N-methyl-D-aspartic acid receptor subunit 2 (anti-NR2) autoantibodies on depression and cognitive dysfunction and their relationships with functional brain connectivity in SLE.

Methods: This cross-sectional study included adult patients who fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology 2019 SLE criteria. Anti-P and anti-NR2 were quantified using ELISA. A 1-hour battery of neuropsychological testing interpreted by a neuropsychologist explored depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D), cognitive domains and quality of life (SF-12). Resting-state functional connectivity (rs-fc) MRI analysis was performed within 1 month, and region-of-interest to region-of-interest (ROI-to-ROI) analyses with the graph theory were performed.

Results: Thirty-three patients with SLE (9% male) were enrolled, mean age (SD) of 43.5 (14) years and median disease duration of 10.4 years (2.9-25.4). Anti-P was positive in 6 (18.2%) and anti-NR2 in 14 (42.4%) patients. Depressive symptoms were found in 14 (42.4%) patients using the CES-D (range 0-51). After correction for age, disease duration, disease activity and white matter lesion load, the CES-D score was independently associated with anti-P serum level (β=0.32; p=0.049) and prednisone daily dose (β=0.38; p=0.023). Nineteen patients (57.6%) showed at least a cognitive test alteration, but no significant association with autoantibodies was found. The rs-fc MRI analysis revealed an independent association between the anti-P serum levels and many altered brain ROI properties but no anti-NR2 and prednisone effects on the cerebral network.

Conclusions: Anti-P was associated with brain network perturbation, which may be responsible for depressive symptoms in patients with SLE.

Keywords: Magnetic Resonance Imaging; antibodies; glucocorticoids; lupus erythematosus, systemic; psychology.

Figure 1

Correlation between CES-D scores and (A) anti-P titre or (B) PDN daily dose (scatter plot). anti-P, anti-ribosomal P protein; CES-D, Center for Epidemiologic Studies Depression; PDN, prednisone.

Figure 2

Results of resting-state functional connectivity MRI analysis on the effect of anti-P serum levels on cerebral networks. The regions with decreased and increased properties are shown in blue and red nodes, respectively (p-FDR<0.05). The node size represents the statistical significance magnitude of the between-group differences in the nodal degree. anti-P, anti-ribosomal P protein; aSMG, supramarginal gyrus anterior division; Cereb, cerebellum; FO, frontal operculum cortex; IC, insular cortex; IFG oper, inferior frontal gyrus pars opercularis; IFG tri, inferior frontal gyrus pars triangularis; l, left; LG, lingual gyrus; MedFC, medial frontal cortex; OFusG, occipital fusiform gyrus; p-FDR, p value corrected for false discovery rate; pPaHC, parahippocampal gyrus; pTFusC, temporal fusiform cortex posterior division; r, right; sLOC, lateral occipital cortex superior division; SubCalC, subcallosal cortex; tolTG, inferior temporal gyrus temporo-occipital part; Ver, vermis.