Background Organ damage may accumulate throughout life. The role of neuropsychiatric lupus manifestations on damage remains unknown. Cognitive dysfunction is present in 17%–66% of patients and an impact on damage accrual is suggested.We found a cognitive deficit association with the presence of anti-dsDNA/methyl-d-aspartate receptor (anti-dsDNA/NMDAR) and anti-ribosomal P proteins (anti-P), antibodies that have fluctuating titers with disease activity. Anti-P exerts neuropathogenic potential through recognition of neuronal surface antigens distributed in regions in memory, cognition and emotion. Anti-neuronal surface P antigen (NSPA), the anti-P target, is involved in neuronal excitatory transmission and mediates anti-P effects on memory dysfunction in mice models
We investigated predictors associated to damage in a SLE cohort with a thorough neuropsychological and antineuronal antibodies baseline assessment, after 4.8 years of follow-up. We include data on a new class of antibodies recognizing NSPA and lacking anti-P reactivity.
Methods From a study on 118 female SLE patients between 2008 and 2013 a subset of 99 SLE patients was followed-up in 2016. Baseline assessment: age, disease duration, therapies and antiphospholipid syndrome (APS). Neuropsychological evaluation: depression (MINI-plus) and cognitive deficit (Cambridge Neuropsychological Test Automated Battery). Antibodies: anti-dsDNA, anti-dsDNA/N-methyl-d-aspartate receptor (dsDNA/NMDAR), anti-P and anti-neuronal surface P antigen (NSPA). Baseline and last follow-up: activity index (SLEDAI-2K), systemic damage index (SDI). Statistics: multivariate analyses.
Results At baseline: mean age (37.0 years; SD 12.7), disease duration (7.2 years; SD 8.2), SLEDAI-2K score (7.4; SD 6.0) and SDI score (0.8; SD 1.3). Major depression (23%), cognitive deficit (18%) and both (3.4%). APS (9%). Antimalarials (84%) and cytotoxics (36%). Anti-dsDNA (49%), dsDNA/NMDAR (19%), anti-P (12%) and anti-NSPA (5%). After a mean follow-up of 4.8 (SD 2.0) years, 11.1% acquired new damage. Final SDI score was 1.0 (SD 1.6). In multivariate analysis baseline SDI, SLEDAI-2K and cytotoxics associated with final damage whereas SLEDAI-2K and cytotoxics associated with accrual damage. Models including anti-NSPA showed its impact on final and accrual damage. Cognitive deficit, depression and other autoantibodies were not damage predictors.
Conclusions Our findings support that disease activity and cytotoxic use are relevant lupus damage predictors. Cognitive dysfunction and depression do not contribute to damage accrual as may fluctuate in lupus patients. A potential influence of anti-NSPA antibodies on damage accrual is proposed.
Funding Source(s): FONDECYT grant # 1160513 to LM and CONICYT Basal grant # AFB170005 to AG
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