To determine the relationship of blood neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in persons with systemic lupus erythematosus (SLE) with and without active major neuropsychiatric (NP) systemic lupus erythematosus (NPSLE)

NPSLE is a poorly understood and heterogeneous manifestation of SLE; more common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes. A likely common end-result of the heterogeneous major syndromes is neuronal/glial injury. Blood NfL and GFAP are promising markers of these in other neurologic diseases; however, they have not yet been evaluated in active major NPSLE (amNPSLE).

In a case-control study, we prospectively enrolled or retrospectively identified patients aged 12-60 years (y) with SLE. Adjudicated cases with and disease controls without amNPSLE were included. Active NPSLE was defined as <6 months from last new/worsening NP symptom. Demographics, clinical data, and serum or plasma biosamples were obtained. Biomarker levels were assessed using the Simoa® Neurology 4-PLEX B assay.

Eleven patients with amNPSLE and 11 age/sex matched SLE controls without amNPSLE (mean age 27.0 vs 27.4 y, 91% female) were included. Major syndromes were non-exclusive, including demyelinating disease (2), autonomic disorder (3), cranial neuropathy (1), seizures (1), myelopathy (1), aseptic meningitis (2), stroke (4), and sensorimotor polyneuropathy (2). Using a generalized linear model, the estimated average blood NfL and GFAP were 4.7 and 59.1 pg/ml, respectively, for SLE controls. Blood NfL was on average 17.4 pg/ml higher (95% CI, 8.0, 37.6; p <0.001), and blood GFAP was 5.7 pg/ml higher (95% CI, 2.7, 12.0; p <0.001) in patients with amNPSLE compared to SLE controls.

Blood NfL and GFAP levels are elevated in persons with SLE with amNPSLE compared to disease matched controls. Larger studies are needed to ascertain their utility in a clinical setting.