Biomarkers in Pediatric Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review

Diagnosis of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (pNPSLE) remains challenging due to NP symptom heterogeneity, lack of specific clinical criteria and validated diagnostic biomarkers, and invasiveness of common diagnostic methods for CNS disease. Although some biomarkers have been identified in adults, their sensitivity, specificity, and clinical applicability in pNPSLE are uncertain. We performed a systematic review according to PRISMA guidelines to evaluate the current evidence on biomarkers associated with pNPSLE. We searched four databases using appropriate search terms for articles in English. After applying our selection criteria, we included 29 studies, from which we manually extracted relevant parameters, including study design, sample size, patient and disease characteristics, biomarker information, and effect sizes. The risk of bias, study quality, and quality of evidence were assessed with standard methods. Most studies had low quality, small samples, and were performed in single centers, which limited the quality of evidence of the biomarkers investigated. Biomarkers showing promising results, with high specificity and sensitivity or predictive value, included CSF neopterin, serum anti-ganglioside M1, a five-biomarker panel including neuronal proteins and anti-ribosomal P, and serum anti-neuronal. Our findings highlight the need for further replication and functional validation studies in pNPSLE.