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Objectives Increased risk for cardiovascular disease (CVD) and neuropsychiatric manifestations are two troublesome areas in systemic lupus erythematosus (SLE). The type I interferon (IFN) system plays a pivotal role in SLE pathogenesis, and is associated with disease activity, disease severity, organ involvement and treatment requirements. An active type I IFN system has been associated with both endothelial dysfunction and neurological damage. We hypothesize that endothelial dysfunction is associated with neuropsychiatric affliction in SLE.This study aimed to assess interferon-associated vascular and neuronal abnormalities and to determine whether vasculopathy correlates with neuronal injury indicated by serum neurofilament light chain (NFL), a neuron-specific protein, which rises in blood and CSF during neuronal damage. Furthermore, to investigate the association of organ damage index with NFL.Methods This cross-sectional cohort study included 147 prevalent SLE patients, age 19-59, attending routine visits at the Department of Rheumatology, Skåne University Hospital, Lund, Sweden. Age and sex-matched healthy controls (n=84) were also included. Vascular function was assessed by peripheral artery tonometry (EndoPAT 2000), where pulse wave amplitude changes in the finger is used to calculate the reactive hyperemia index (RHI) and augmentation index (AI). NFL and IFN were analyzed in serum using electrochemiluminescence immunoassay. Demographic and clinical data were obtained from research registries. Univariate and multiple linear regression, including age and sex adjustment, were used.Results SLE patients, had compared with healthy controls, significantly higher levels of NFL in serum and increased AI. Patients with elevated IFN-alpha had lower RHI (p=0.009), higher AI (p=0.026), and higher concentration of serum NFL (p=0.025), compared to patients with low levels of IFN-alpha. Organ damage index of 1 or higher (p=0.006) was independently associated with increased NFL. Neither RHI nor AI were associated with NFL.Abstract PO:09:237 Figure 1A) reactive hyperemia index (RHI), B) augmentation index (AI) and C) neurofilament light chain (NFL) in patients with SLE, stratified by interferon high (n=45) and low (n=102). Univariate linear regression using RHI, AI or NFL as outcome of IFNa high or low levels in serum, adjustment for age and sexConclusions SLE patients with elevated IFN-alpha demonstrate vascular changes, including impaired endothelial function and greater arterial stiffness, and elevated NFL, indicative of neuronal injury. Vascular function, assessed with peripheral artery tonometry, were not associated with NFL concentrations. Increased NFL is multifactorial; while our results do not support vasculopathy as a mediator, its contribution to neuronal damage in SLE cannot be excluded.