Background Neuropsychiatric manifestations areconsidered to be a serious complication in systemic lupus erythematosus (SLE).The pathogenesis of neuropsychiatric manifestations has been attributed to autoantibody-mediated neural dysfunction.
Objectives To investigate the prevalence and associations of neuropsychiatric manifestations and serum biomarkers in SLE.
Methods We included consecutive SLE followed at the rheumatology unit of the State University of Campinas. Neurological manifestations were analyzed according to the ACR classification criteria. Mood disorders were determined through Becks Depression and Anxiety Inventory in all participants. 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. Total dose of corticosteroids and other immunosuppressant medications used since the onset of disease were calculated by data obtained by careful review of the medical charts.Serum biomarkers (S100β, NF-H and antiribossomal P (Anti-P) and anticardiolipin antibodies levels were measured by enzyme-linked immunosorbent assay using commercial kits from BioVendor, Inc (Czech Republic). Anti-double stranded DNA (dsDNA) antibodies were determined by indirect immunofluorescence using Crithidia as substrate and considered positive if ≥1:20.Precipitating antibodies to extractable nuclear antigens (ENAs),including Ro (SSA), La (SSB), and Sm were detected by a standardizedELISA method, and considered positive if higher than 1:40. Data were compared by non-parametric tests.
Results We included 146 SLE patients (138 women; mean age of 26.60±13.42 years; range 9-67). The mean disease duration was 8.13±7.05 years (range 0-39 years). At time of study entry, 50 (34.24%) SLE patients had active disease (mean SLEDAI scores3.68±3.97; range 0-14). Forty (27.39%) cSLE had cumulative damage (mean SDI scores 0.68±1.04; range0-4). We observed neuropsychiatric manifestations in 59 (40.41%) SLE. The most frequent manifestations observed in our cohort were anxiety (43.83%), headache (39.04%), depression (34.24%) and seizure (11.64%). We observed an association between neuropsychiatric manifestations and antiribosomal P protein (p=0.001), aCL (p=0.012) and LA (p<0.001). In the analyses of each individual manifestation, anxiety was associated with antiribosomal P protein (p=0.003) and anti-Smith (p=0.010), headache with antiribosomal P protein (p<0.001) and LA (p=0.006) and depression was associated with antiribosomal P protein (p=0.031).
Conclusions Autoantibodies such as antiribosomal P protein antibodies, aCL and LA, anti-Ro, anti-dsDNA and anti-Smith are associated with neuropsychiatric manifestations in SLE, suggesting the autoantibodies pathway in neural dysfunction in SLE.
Acknowledgements Grants: Research Support Foundation of São Paulo –FAPESP (Simone 2008/02917-0, Mariana 2011/03788-2, Aline 2013/09480-5) CNPQ (300447/2009-4 and 471343/2011-0; 302205/2012-8; 473328/2013-5)
Disclosure of Interest None declared