Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: The role of innate immunity in the pathogenesis of Systemic Lupus Erythematosus (SLE) has acquired increasing importance lately. Chronic Granulomatosus Disease (CGD), a hereditary inability of phagocytes in producing Reactive Oxygen Species (ROS), has been associated with increased frequency of discoid lupus erythematosus (2.7%) and with SLE (0.5%). This study aimed to evaluate the oxidative response in monocytes and neutrophils from SLE patients and healthy controls (HC) at basal state and after bacterial stimulus.
Methods: 300 SLE patients and 301 age- and gender-paired HC (blood donors) were clinically examined and evaluated for quantification of the oxidative burst in phagocytes by flow cytometry based on the oxidation of 2,7-dichlorofluorescein-diacetate before and after stimuli with Staphilococcus aureus and Pseudomonas aeruginosa. There was a 7-day wash-out period for immunosuppressant drugs before sample collection.
Results: No patient or HC presented oxidative burst profile compatible with CGD, however one patient was classified as carrier of defective gene (0.33%). SLE neutrophils had higher basal oxidative activity than HC [mean fluorescence intensity (MFI)=53.77±11.38 versus 15.08±2.63, respectively; p<0.001]. ROS production was also significantly higher in SLE as compared with HC after stimulation with S. aureus (MFI=355.46±58.55 versus 151.92±28.25, respectively; p<0.001) or P. aeruginosa (MFI=82.53±10.1 versus 48.99±6.74, respectively, p<0.001). Furthermore, the neutrophilic response after bacterial stimuli (DMFI = post-stimulus MFI minus basal MFI) was more intense in SLE than in HC (S aureus: 301.69±54.42 versus 118.38±26.03, respectively; p<0.001; P aeruginosa: 28.76±12.3 versus 15.45±5.15, respectively; p<0.001). Oxidative burst profile was not associated with disease activity (SLEDAI≥6) or severity (SLICC-DI≥2). Neutrophil basal ROS production was higher in patients with lupus nephritis (median MFI=39.43; ranging from 1.0 to 167.4) than in patients without nephritis (median MFI=27.29; ranging from 1.2 to 143.9; p=0.014). In addition neutrophils from patients with lupus nephritis (n=166) presented higher increment in ROS production after stimulus with S. aureus (median DMFI=320.1; ranging from 194.9 to 826.1) than neutrophils from patients without nephritis (n=133; median DMFI=278.5; ranging from 149.9 to 649.9; p=0.03). These differences in ROS production were not observed in monocytes from patients with lupus nephritis. There was no association of PMN oxidative burst profile and the therapeutic regimen.
Conclusion: Neutrophils from SLE patients presented increased basal ROS production and increased oxidative response to bacterial stimuli. These findings were particularly evident in patients with kidney involvement. The present findings corroborate the important role of innate immunity in SLE and implicate neutrophils in the pathophysiology of the disease.
Disclosure:
S. F. Perazzio,
None;
R. Salomao,
None;
N. P. Silva,
FAPESP,
2;
L. E. C. Andrade,
Fleury Medicine and Health Laboratories,
5.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-oxidative-burst-in-neutrophils-but-not-monocytes-in-systemic-lupus-erythematosus/