ObjectiveTo examine select brain-reactive proteins for their usefulness to serve as blood-based biomarkers in the screening for neurocognitive deficits in childhood-onset systemic lupus erythematosus (cSLE-NCD).MethodsPatients withcSLE (n=40) were studied longitudinally (month 1; month 18): working memory, psychomotor speed and visuoconstructional ability were assessed using formal neurocognitive testing to determine the presence of cSLE-NCD. Patients also completed the computerised Paediatric Automated Neuropsychological Assessment Metrics. The following brain-reactive proteins were measured in the blood: neutrophil gelatinase associated lipocalin (NGAL), S100B, S100A8/9, antibodies to NR2 glutamate receptor (aNR2-AB), ribosomal-P (aP-AB), glycoprotein-1 (aGP1-AB), and lupus anticoagulant.ResultscSLE-NCD was present in 6 of 40 patients at baseline and 4 of 27 patients with 18-month information. aP-AB positivity was more commonly present with cSLE-NCD than without (p=0.05). aP-ABs were negatively associated with performance on tests assessing working memory, psychomotor speed and visuoconstructional ability in using formal neurocognitive testing. There were also significant negative associations between aP-AB, S100A8/9, aNR2-AB, aGP1-AB, and lupus anticoagulant and accuracy rates on select Paediatric Automated Neuropsychological Assessment Metrics subtests (p<0.05). Over time, decline in cognitive performance was more pronounced among patients with higher NGAL and aNR2-AB levels. Combinations of serum levels of S100A8/9, S100B, NGAL, aNR2-AB and aP-AB were able to identify cSLE-NCD (sensitivity: 100%; specificity 76%) in exploratory analysis.ConclusionsSelect brain-reactive proteins in the blood are associated with cognitive performance and the presence of cSLE-NCD, cross-sectionally and over time. This raises the possibility that testing of these proteins may assist with the screening of cSLE-NCD.

Objective To assess the quality of medical care in childhood-onset systemic lupus erythematosus (cSLE) at tertiary pediatric rheumatology centers as measured by observance cSLE quality indicators (cSLE-QI). Methods International consensus has been achieved for cSLE-QI (Hollander et al. Arthritis Care & Research, 2013) capturing medical care provision in nine domains: diagnostic testing, education of cardiovascular (CV) risk and lifestyles, lupus nephritis (LN), medication management, bone health, ophthalmological surveillance, transition, pregnancy and vaccination. Using medical record information, the level of performance these cSLE-QI was assessed in cSLE populations treated at four tertiary pediatric rheumatology centers in the U.S, two in Brazil, and one center in India. Results A total of 483 cSLE patients were assessed. Care for the 310 U.S. patients differed markedly for cSLE-QI addressing LN, bone health, vaccinations, education on CV risk, and transition planning. Performance of safety blood testing for medications was high at all centers. Despite often similar performance on the cSLE-QI, access to kidney biopsies was lower in Brazil than in the U.S. Irrespective of country of practice, larger centers tended to meet the cSLE-QI more often than smaller centers. Conclusions The cSLE-QI, evidence based minimum standards of medical care, are not consistently met in the U.S. or some other countries outside the U.S. This has the potential to contribute to suboptimal cSLE outcomes.

Objectives To use diffusion tensor imaging (DTI) for investigating white matter connectivity changes associated with neurocognitive dysfunction in childhood-onset lupus (cSLE-NCD) as measured by formal neuropsychological testing. Methods DTI was performed in six subjects with (cSLE-NCD) and nine without neurocognitive dysfunction (cSLE-noNCD) as well as 14 healthy controls. Presence of neurocognitive deficits were identified by formal neuropsychological testing. The brain was divided into 116 regions, and pairwise connectivity (defined as the number of streamlines with an endpoint in each of those regions) and streamline density (defined as the number of streamlines passing through a region regardless of endpoints) were evaluated. Group comparisons were made for regional and global measures of streamline density and pairwise connectivity. Results A significant decrease in global streamline density was observed in the cSLE-NCD vs. control group (1189 vs. 1305 p = 0.002) and vs. cSLE-noNCD (1189 vs 1320 p= 0.001). The cSLE-noNCD and control groups had similar streamline density. A similar pattern for pairwise connectivity was observed with significant decrease in the cSLE-NCD group (217) versus the cSLE-noNCD (236; p=0.013) and control group (238; p=0.004). Regional measures of pairwise connectivity displayed mixed results. Conclusions The analysis of DTI in this pilot study shows cSLE-NCD is associated with global loss of streamline density and pairwise connectivity suggesting breakdown of the structural network. These results complement previously reported functional and volumetric findings that suggest cSLE-NCD is associated with measurable changes in gray and white matter. If confirmed in larger cohorts, DTI abnormalities could be used as imaging biomarkers of cSLE-NCD.

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