Methods: As part of a larger study, the cognitive ability of 38 patients with cSLE was studied using the cSLE Battery of Neuropsychological Tests (Ross et al; 2008) that probes cognitive domains typically impaired with cSLE, with overall cognitive performance expressed as the average z-scores of the standardized tests (mean in healthy reference population= 0; standard deviation= 1). Serum levels of neutrophil gelatinase associated lipocalin (NGAL; involved in blood-brain barrier integrity), as well as auto- antibodies to NR2 (involved in neuronal plasticity and apoptosis); phospholipids (aPL) (associated among others with white matter hyperdensities on magnetic resonance imaging and thrombosis), and ribosomal-P (associated with depression and seizure; proposed involvement in neuronal apoptosis) were measured using commercially available standard assays.

Results: The overall level of cognitive function was significantly worse in those with cSLE who tested positive for aPL-antibodies as compared to aPL-antibody negative cSLE patients [mean+SE; -2.44± 1.13 vs. -0.38± 0.61; p= 0.041]. We found aPL antibodies to be associated with a 5-fold increased risk of NCD (40% vs. 12%; p =0.08). We also found anti-ribosomal P antibodies present in 67% (24/38) of the cSLE patients. As shown in Figure 1, those who tested positive for anti-ribosomal P antibodies had a significantly lower overall cognitive functioning vs. cSLE patients without anti-ribosomal P antibodies (p= 0.0006). Conversely, we found serum levels of anti-NR2 antibodies to be unrelated to cognitive ability. The same was true for serum levels of NGAL.

Conclusion: Presence of aPL and anti-ribosomal P antibodies in the serum is associated with the level of cognitive ability of children with cSLE, providing proof-of principle that discovery of biomarkers for NPSLE in the blood is feasible. Additional research is necessary to assess whether the duration of antibody exposure and/or the combination of antibodies are suited to reliably identify patients who suffer from cSLE-associated NCD or are at risk of developing it.