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Biomarkers in Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Literature Review of the Last Decade.

ABSTRACT: Nervous system involvement in patients with SLE, termed neuropsychiatric SLE (NPSLE), constitutes a diagnostic challenge, and its management is still poorly optimised. This review summarises recent insights over the past decade in laboratory biomarkers of diagnosis, monitoring, and prognosis of NPSLE. An initial systematic search in the Medline and Web of Science was conducted to guide the selection of articles. Emerging diagnostic biomarkers in NPSLE that displayed satisfactory ability to discriminate between NPSLE and controls include serum interleukin (IL)-6, microRNA (miR)-23a, miR-155, and cerebrospinal fluid (CSF) α-Klotho. CSF lipocalin-2, macrophage colony-stimulating factor (M-CSF), and immunoglobulin (Ig)M also displayed such ability in two ethnically diverse cohorts. Serum interferon (IFN)-α and neuron specific enolase (NSE) were recently reported to moderately correlate with disease activity in patients with active NPSLE. CSF IL-8, IL-13, and granulocyte colony-stimulating factor (G-CSF) exhibited excellent sensitivity, yet poorer specificity, as predictors of response to therapy in patients with NPSLE. The overall lack of validation studies across multiple and diverse cohorts necessitates further and well-concerted investigations. Nevertheless, we propound CSF lipocalin 2 among molecules that hold promise as reliable diagnostic biomarkers in NPSLE.

SUBMITTER: Lindblom J

PROVIDER: S-EPMC8869794 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Biomarkers in Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Literature Review of the Last Decade.

Lindblom Julius J Mohan Chandra C Parodis Ioannis I

Brain sciences 20220130 2

Nervous system involvement in patients with SLE, termed neuropsychiatric SLE (NPSLE), constitutes a diagnostic challenge, and its management is still poorly optimised. This review summarises recent insights over the past decade in laboratory biomarkers of diagnosis, monitoring, and prognosis of NPSLE. An initial systematic search in the Medline and Web of Science was conducted to guide the selection of articles. Emerging diagnostic biomarkers in NPSLE that displayed satisfactory ability to discr ...[more]

PMID: 35203955

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Project description:IntroductionBelimumab is a recombinant human monoclonal antibody that binds to soluble B-lymphocyte stimulator and inhibits its biological activity. Since receiving approvals for the treatment of systemic lupus erythematosus (SLE), several observational studies have investigated the effectiveness of belimumab in the real-world setting. This study reports a systematic review and meta-analysis of the literature to evaluate the real-world effectiveness of belimumab for the treatment of SLE.MethodsA literature search following PRISMA Guidelines and limited to studies in English was performed (2014-2020) to identify relevant studies reporting effectiveness outcomes of belimumab in patients with SLE. A modified version of the Newcastle-Ottawa Scale was used to assess study quality. Outcomes, including SLE Disease Activity Index (SLEDAI) score, prednisone-equivalent use, and SLE flare were pooled and analyzed using statistical aggregation methods.ResultsThe literature search identified 514 articles for initial review. Of these, 17 articles were suitable for data extraction and summary. Baseline characteristics of patients in real-world studies were generally similar to those of relevant clinical trials, including age, sex, disease duration, SLEDAI score, and prednisone-equivalent use. Real-world use of belimumab was associated with reductions in SLEDAI score (mean baseline score to month 6: 10.1-4.4; 57% reduction), prednisone-equivalent dosing (mean baseline dose to month 6: 12.1 mg/day to 6.9 mg/day; 43% reduction), and flare frequency (12 months prior to belimumab to 12 months after belimumab: 1.15-0.39 mean flares per patient per year; 66% reduction). Long-term data (up to 2 years post-treatment initiation) for SLEDAI score and prednisone-equivalent dose indicated that improvements in both outcomes continue over time among patients remaining on therapy.ConclusionsIn the real-world setting, observed outcomes with belimumab for the treatment of SLE are consistent with those reported from randomized clinical trials. Improvements persist long-term for SLEDAI activity and prednisone-equivalent use with belimumab.

Project description:IntroductionThe pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined.MethodsTo identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s).ResultsWe enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients' sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients' sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-β2-glycoprotein-I (aβ2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies.ConclusionIn conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include β2GPI.

Dataset Information

Biomarkers in Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Literature Review of the Last Decade.

Publications

Biomarkers in Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Literature Review of the Last Decade.

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