{
  "abstract": "Objectives Neurofilament light chain (NfL), a validated biomarker of neuronal injury, has emerged lately as a promising biomarker for neuropsychiatric SLE (NPSLE). Interferon (IFN)-alpha is a crucial mediator in SLE and potentially contributes to pathogenesis of NPSLE. Thus, we investigated associations between serum NfL, IFN-alpha, disease activity and neuropsychiatric symptoms in SLE and examined the effects of IFN-alpha and IFN receptor blockade on NfL release in a neuronal cell line.Methods A total of 270 patients fulfilling the 1997 SLE classification criteria were recruited consecutively at the Rheumatology Clinic at Uppsala University Hospital, Sweden. In addition, 89 healthy blood donors, matched for age and sex were included. SLE Disease Activity (SLEDAI), Systemic Lupus Activity Questionnaire (SLAQ) and clinical data were collected at the time of sampling. A human neuroblastoma cell line SK-N-SH was cultured with IFN-alpha2b (Introna), with or without anifrolumab or control antibody for 72 hours. NfL and IFN-alpha levels were measured in serum and cell cultures supernatants, using SIMOA immunoassay. Linear regression analysis was used to assess IFN-alpha and disease activity indices as possible predictors of serum NfL. P-values <0.05 were considered significant.Results Serum NfL levels were significantly elevated in patients with SLE compared with healthy controls (median= 13.9(2.5-737.9) vs. 8.7(2.6-42.1) pg/mL; p<0.001). In linear regression models adjusted for age and creatinine, higher levels of IFN-alpha, SLEDAI, and SLAQ scores were independently associated with increased NfL (p= 0.002, <0.001 and 0.01, respectively). Moreover, both neuro-psychological SLAQ subscore and self-reported cognitive symptoms (depression and forgetfulness) were significantly associated with higher NfL levels (p=0.03 both). In vitro, IFN-alpha exposure for 72 hours significantly increased NfL concentrations in the supernatant of a neuronal cell line, figure 1. This effect was markedly attenuated by the addition of anifrolumab.Abstract PO:09:241 Figure 1Concentration of neurofilament light (NfL) in SK-N-SH cell cultures in the presence of various concentrations of IFN-alpha2b (Introna) with or without anifrolumab or control antibody for 72 hoursConclusions IFN-alpha is associated with serum NfL in SLE and induces NfL release in neuronal cells which is attenuated by anifrolumab. Our findings propose a role for type I IFN in neuronal injury and suggest that anifrolumab therapy should be evaluated against NPSLE. Additional action is required in the management of SLE patients with high disease activity and self-reported cognitive symptoms as they may indicate neuronal damage.",
  "authors": [
    {
      "affiliations": [
        "Uppsala University, Department for Medical Sciences, Rheumatology, Uppsala, Sweden"
      ],
      "name": "Ioanna Giannakou"
    },
    {
      "affiliations": [
        "Uppsala University, Department for Medical Sciences, Neurology, Uppsala, Sweden"
      ],
      "name": "Joachim Burman"
    },
    {
      "affiliations": [
        "Uppsala University, Department for Medical Sciences, Rheumatology, Uppsala, Sweden"
      ],
      "name": "Lars Rönnblom"
    },
    {
      "affiliations": [
        "Uppsala University, Department for Medical Sciences, Rheumatology, Uppsala, Sweden"
      ],
      "name": "Maija-Leena Eloranta"
    },
    {
      "affiliations": [
        "Uppsala University, Department for Medical Sciences, Rheumatology, Uppsala, Sweden"
      ],
      "name": "Dag Leonard"
    }
  ],
  "title": "PO:09:241 Interferon-alpha–associated elevation of neurofilament light chain in SLE and its inhibition by anifrolumab in vitro",
  "uid": "c72244da-64b5-59ad-a96f-5f819677e0fe"
}