Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) biomarkers

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) represents one of the most heterogeneous, clinically challenging, and immunologically complex manifestations of SLE. Affecting up to 40% of patients with SLE, neuropsychiatric involvement encompasses a broad spectrum of central and peripheral nervous system disorders - ranging from cognitive dysfunction and mood disturbances to psychosis, seizures, and cerebrovascular disease - many of which remain inadequately understood, inconsistently classified, and therapeutically underserved.At the core of NPSLE pathogenesis lies a highly orchestrated, yet dysregulated, immune response. Autoantibodies - including anti-double-stranded DNA (anti-dsDNA), anti-N-methyl-D-aspartate receptor (anti-NR2), anti-ribosomal P, and antiphospholipid antibodies - have been implicated in direct neuronal targeting and blood-brain barrier (BBB) disruption. Equally, some soluble serum mediators such as S100A8/A9 (calprotectin) and MMP-9 have emerged as candidate biomarkers distinguishing patients with cognitive impairment from those without, offering a window into the neuroinflammatory state that standard clinical assessments cannot yet capture.Yet despite these advances, critical gaps persist. The immune mechanisms that determine which patients will develop neuropsychiatric manifestations - and how severe, reversible, or progressive those manifestations will be - remain poorly defined. Attribution of NP events to SLE versus comorbid processes continues to challenge diagnosis. Validated, immune-anchored biomarkers for early detection are absent from routine clinical practice. And in pediatric populations, the additional vulnerability of a developing brain to immune dysregulation introduces an entirely distinct dimension of long-term neurodevelopmental risk that has only recently begun to receive the scientific attention it warrants.This Research Topic invites original research articles, systematic reviews, and translational perspectives that address the immunological underpinnings of neuropsychiatric manifestations in SLE. Submissions should provide mechanistic insight into how immune and autoimmune processes drive neuropsychiatric outcomes, and should speak to the prevention, diagnosis, or treatment of these conditions. We particularly welcome work in the following areas:• Autoantibody profiling and neuropsychiatric attribution in SLE: identification and validation of autoantibody signatures (anti-NR2, anti-ribosomal P, antiphospholipid antibodies, ANAs) as biomarkers for NPSLE phenotypes, disease activity, and clinical trajectory.• Serum and soluble immune mediators in neuroinflammation: roles of alarmins (S100A8/A9), matrix metalloproteinases, cytokines, and complement components in cognitive impairment and other neuropsychiatric manifestations in SLE and related disorders.• Cognitive dysfunction as an NPSLE outcome: novel approaches to phenotyping, subtyping, and tracking cognitive impairment in SLE, including neuropsychological testing, neuroimaging, and multi-omics biomarker integration.• Brain-immune axis in pediatric autoimmune disease: immune mechanisms underlying neuropsychiatric morbidity in childhood-onset SLE (cSLE) and other pediatric rheumatologic conditions, including the impact on brain development, mental health trajectories, and long-term neurocognitive outcomes.• Biomarker discovery for early detection and treatment stratification: identification of pre-clinical or early-phase immune signatures predictive of neuropsychiatric involvement, enabling timely intervention.• Therapeutic implications of immune mechanisms: translational work linking immune pathways to therapeutic targets for the prevention or management of NPSLE and related neuropsychiatric autoimmune disorders.Scope note: Manuscripts focused exclusively on neuroimaging or ultrasound methodology, without providing mechanistic insight into immune-related processes that yield outcomes relevant to the prevention, diagnosis, or treatment of NPSLE, fall outside the scope of Frontiers in Immunology and will not be considered for this Research Topic. ABOUT THE EDITORS: This Topic brings together a multidisciplinary editorial team whose combined expertise spans early SLE biomarker discovery and IgG sialylation (Muñoz-Grajales), disease activity measurement and the immunology of cognitive dysfunction in SLE (Touma), pediatric neuroimmunology and brain-immune axis research in childhood rheumatologic disease (Knight), and the full clinical and immunological spectrum of NPSLE, NMOSD, and autoantibody-driven psychiatric phenotypes (Fujieda). Together, this panel is uniquely positioned to consolidate a rapidly evolving field and to define the immune mechanisms that will underpin the next generation of diagnostic and therapeutic strategies for neuropsychiatric autoimmune disease. COI declaration: Dr. Fujieda declares have received research grants from MBL, Taisho, and AstraZeneca Topic editors: Carolina Muñoz Grajales, Yuichiro Fujieda, Zahi Touma, Andrea Knight Source: https://www.frontiersin.org/research-topics/81016/neuropsychiatric-systemic-lupus-erythematosus-npsle-biomarkers