Background/Purpose: Cognitive impairment is common in over 50% of SLE patients with active neurological and psychiatric disorders. Cytokine dysregulation and inflammation are mechanisms that may underlie cognitive impairment. TNF-α leading to inflammatory brain disease may result in cognitive impairment in childhood-onset systemic lupus erythematosus (cSLE). Objective: To determine if increased sera TNF-α levels are associated with cognitive impairment in cSLE. 

Methods: We included 57 SLE patients (women 52; mean age 17.51±4.37; range 9-30) and 65 healthy (women 60; mean age 18.93±65.95; range 6-32) age and sex matched controls. Cognitive evaluation was performed in all participants using Wechsler Intelligence Scale for children (WISC-III) and Wechsler Intelligence Scale for adults (WAIS), according to age and validated in Portuguese. Mood disorders were determined through Becks Depression and Anxiety Inventory in all participants. SLE patients were further assessed for clinical and laboratory SLE manifestations, disease activity [SLE Disease Activity Index (SLEDAI)], damage [Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)] and current drug exposures. Total dose of corticosteroids and other immunosuppressant medications used since the onset of disease were calculated by data obtained by careful review of the medical charts. Sera samples were obtained from all participants in the absence of infections. TNF-α levels were measured by enzyme-linked immunosorbent assay using commercial kits from R&D Systems. Mann-Whitney Test was used to compare TNF-α concentrations between groups. Multivariate analysis was performed including sex, age, SLE duration, disease activity, and cumulative damage, cognitive impairment and current drug exposures. A P value of <0.05 was considered statistically significant.

Results: Sera TNF-α levels were increased in cSLE (3.39±5.57pg/mL) when compared to healthy controls (1.54±0.92pg/mL) (p=0.015). Cognitive impairment was identified in 28 (49.12%) cSLE and in 6 (9.23%) healthy controls. Sera TNF-α levels were increased in cSLE patients (4.64±1.52pg/mL) with cognitive impairment compared to cSLE patients without cognitive impairment (1.52±0.75pg/mL) (p=0.03). No significant difference in TNF-α levels between cSLE patients without cognitive impairment and controls was observed (p=0.76).  No association between TNF-α levels and other clinical, laboratory variable, SLEDAI and SDI scores was observed. In the multivariate analysis, sera TNF-α levels were independently associated with cognitive impairment (OR=3.84; 95%CI 2.39-5.71).

Conclusion: Sera TNF-α levels are elevated in cSLE patients with cognitive impairment. TNF-α were independently associated with cognitive impairment. Our findings support the neuromodulator role of TNF-α in brain activity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tnf-%ce%b1-is-associated-with-cognitive-impairment-in-childhood-onset-systemic-lupus-erythematosus/