Predictors of damage accrual in systemic lupus erythematosus: a longitudinal observational study with focus on neuropsychological factors and anti-neuronal antibodies

Objective: Central nervous system disease occurs in over 20% of patients with systemic lupus erythematosus (SLE) resulting in major morbidity and damage. Cognitive dysfunction is common in SLE, but the cause remains uncertain and treatment options are limited. This study explores the influence of clinical, neuropsychological factors and anti-neuronal antibodies on lupus damage accrual. Method: A prospective cohort with 99 SLE patients recruited between 2008 and 2013 and followed up in 2016 was established. Baseline evaluations were depression (MINI-Plus), cognitive function evaluating attention, visuospatial memory and executive functions, and anti-neuronal antibodies. Activity index (SLEDAI-2K) and SLICC/ACR Damage Index (SDI) were assessed at baseline and last follow-up. Results: At baseline, median (interquartile range) age was 36.0 years (27.0–45.0), disease duration 3.7 years (0.4–12.4), SLEDAI-2K 6.0 (3.0–12.0), and SDI score 1.0 (0–1.0). Major depression was present in 23%, cognitive deficit in 18%, and received immunomodulators in 36%. Anti-dsDNA/N-methyl-d-aspartate receptor antibodies were present in 19%, anti-ribosomal P in 12%, and anti-neuronal surface P antigen (NSPA) in 5%. After a median follow-up of 55 months (interquartile range 39–78), 11% had damage accrual. In a multivariate analysis, baseline SDI, SLEDAI-2K, and immunomodulators use were associated with final damage, whereas SLEDAI-2K and immunomodulator use were also associated with accrual damage. Models including anti-NSPA showed impact on final and accrual damage. Cognitive deficit, depression, and other autoantibodies were not predictors. Conclusions: Disease activity and immunomodulator use associate with lupus damage. Of the anti-neuronal antibodies examined, anti-NSPA emerged as a potential poor prognostic factor, probably related to severe SLE onset requiring elevated corticosteroid doses.Key Points• Anti-NSPA may be a worse prognostic factor in SLE.• Other neuropsychological factors do not influence damage.