Abstract

BackgroundThe pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is multifactorial and involves diverse cytokines, autoantibodies and immune complexes inducing blood-brain barrier (BBB) dysfunction, neuroendocrine-immune imbalance, vascular occlusion, tissue, and neuronal damage. Several pro-inflammatory cytokines have been implicated in the pathogenesis of NPSLE [1]. Previously we have shown that the titer of anti-suprabasin (SBSN) antibodies in cerebrospinal fluid (CSF) of NPSLE patients was significantly higher than in SLE, MS and NPH groups [2]. However, distinguishing NPSLE from other neuropsychiatric conditions with different etiologies is challenging.ObjectivesThis study determined the most critical serum biomarkers for the development of NPSLE as they may have clinical utility prior to the onset of neuropsychiatric symptoms.MethodsWe retrospectively analyzed 35 NPSLE patients, 34 SLE patients, 20 viral meningitis (VM) patients, and 16 relapsing-remitting multiple sclerosis (MS) patients. We measured anti-SBSN antibodies concentrations in serum by using Luciferase immunoprecipitation system (LIPS) assay. The serum concentrations of cytokines/chemokines were measured by using multiplex bead-based assay. All the clinical information and laboratory tests were collected at the time of admission.ResultsThe Bayesian posterior mean and 95% HPDI of the cut-off of AI and its PPV and 1-NPV values were 5.26 (3.68;7.17), 0.87, (0.72; 1.0) and 0.44, (0.36; 0.5), respectively (Figure 1).Figure 1.Summary of the posterior distribution of the cutoff of AI and its predictive value (1-NPV and PPV). The 95% HPDI is shown as the thick black horizontal line with the boundaries written above the lineAmong analyzed biomarkers, VEGF had the highest sparsity-oriented important learning (SOIL) importance, followed by AI, sCD40L, IL-10, GRO, MDC, IL-8, IL-9, TNFα, MIP-1α (Figure 2).Figure 2.Top 10 biomarkers having highest SOIL importance in prediction of NPSLE.Abbreviations• AI: anti-SBSN antibody index• PPV: positive predictive• NPV: negative predictive value• SOIL: sparsity-oriented important learning• IL: interleukin•MIP: macrophage inflammatory protein• sCD40L: soluble CD40 ligand• MDC: macrophage-derived chemokine• VEGF: vascular endothelial growth factor• MDC: macrophage-derived chemokine• TNF: Tumor necrosis factorConclusionOur data demonstrated the ranking of serum biomarkers for the prediction of NPSLE. The most essential biomarkers are VEGF, anti-SBSN antibodies, sCD40L, IL-10, GRO, MDC, IL-8, IL-9, TNFα, MIP-1α.

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