Background/Purpose: Autoantibodies and auto reactive B cells participate on the pathogenesis of systemic lupus erythematosus (SLE), affecting various organs and tissues, including the nervous system, referred as neuropsychiatric SLE (NPSLE). The B-lymphocyte stimulator (BLyS) cytokine, which induces B cell proliferation and survival, may play an important role in NPSLE manifestations. In this study, we examine BLyS levels in SLE patients with well-defined NPSLE symptoms as compared to SLE patients without NPSLE and individuals with depression and cognitive impairment and healthy controls.

Methods: We included 75 SLE patients from the Rheumatology outpatient unit and 53 age and sex matched controls (20 with primary depression, 14 with mild cognitive impairment and 9 healthy controls). SLE patients were selected based on the presence of depression (N=25), cognitive impairment (N=25) or absence of neuropsychiatric (NP) manifestations (N=25). SLE patients that have been prescribed belimumab or rituximab were excluded. SLE patients and controls had similar age and sex distribution. A complete clinical, laboratory and neurological evaluation was performed in all subjects. Mood disorders were determined through Beck Depression (BDI)). Cognitive evaluation was evaluated by Automated Neuropsychological Assessment Metrics (ANAM), Montreal Cognitive Assessment (MoCA) and formal cognitive testing. BLyS concentrations were evaluated in serum samples with Quantikine Elisa (R&D Systems, USA), following the manufacturer’s instructions and with minimum detectable levels of2.68 pg/mL. All measurements were made on a single occasion. Data were analysed using the Mann-Whitney U test, with a p value < 0.05 considered significant.

Results: Active disease was observed in 23 (30.7%) SLE patients. Seventy (93%) were on immunosuppressant medication [Prednisone with doses ≥7.5 mg/day in 55 (73%), hydroxychloroquinein 57 (76%), azathioprine in 30 (40%), mycophenolate in 20 (26%). BLyS serum concentrations were significantly increased in SLE patients when compared to controls (p=0.005). BLyS serum concentration from 25 individuals with SLE and depression were significantly increased when compared to 25 SLE without NP manifestations (p=0.042), and the 20 healthy individuals with primary depression (p=0.017). No significant difference between primary depression and healthy controls was observed. BLyS serum concentration from 25 individuals with SLE and cognitive impairment were significantly increased when compared to 25 SLE without NP manifestations (p=0.003), and the 14 healthy controls with mild cognitive impairment (p=0.016). No significant difference between mild cognitive impairment controls and healthy controls was observed.

Conclusion: SLE patients with depression and cognitive impairment had higher BLyS levels when compared to SLE patients without NP manifestations and healthy controls with NP diagnoses. BLyS may play a role in NPSLE pathogenesis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/blys-levels-are-elevated-in-systemic-lupus-erythematosus-patients-with-neuropsychiatric-manifestations/