Session Title: Vasculitis III
Session Type: Abstract Submissions (ACR)
Background/Purpose: Behçet’s disease (BD) exhibits several features suggestive of neutrophil hiperactivity. It is unclear whether neutrophil activation occurs constitutively or if it is secondary to yet unknown stimuli. Previous studies suggested a possible role for infectious agents and for unknown plasma factors in BD pathogenesis. The present study investigated the oxidative burst in phagocytes of patients with active BD (aBD) and inactive BD (iBD) in the presence of diverse stimuli.
Methods: Neutrophils and peripheral blood mononuclear cells (PBMC) were obtained from patients with aBD (n=30), iBD (n=31), septic patients (SP; n=25), and healthy controls (HC; n=30). BD activity was established as Behçet’s Disease Current Activity Form Simplified (BDCAFs) score≥2. Oxidative burst was assessed by dihidrorhodamine (DHR) oxidation before and after stimulation with phorbol myristate acetate (PMA) or human plasma (from HC or aBD). H2O2 and O2– production was determined in neutrophils and PBMC by luminol/lucigenin luminescence intensity with or without stimulation with PMA, Streptococcus pneumoniae, Streptococcus sanguinis, Candida albicans or human plasma.
There was no significant difference in medication use between aBD and iBD patients. Resting phagocytes from the four groups presented equivalent oxidative burst (DHR assay and H2O2/O2– production). However, aBD neutrophils produced more O2– when exposed to aBD plasma (median/range=96,297/19,202-298,941) compared to HC plasma (48,831/4,001-105,848; p=0.028) or non-stimulated (5,721/551-23,838; p<0.01). HC neutrophils also produced more O2– when stimulated by aBD plasma (93,452/12,242-226,932) versus HC plasma (36,225/8,432-79,461; p=0.028) versus non-stimulated (3,387/1,870-13,935, p<0.01). aBD neutrophils also produced more H2O2 when exposed to aBD plasma (404,045/24,825-1,408,347) compared to HC plasma (338,238/5,042-745,653; p=0.02) or non-stimulated (9,300/2,706-27,193; p<0.01). The same occurred with neutrophils from HC: aBD plasma (355,079/51,354-513,977); non-stimulated (15,092/4,959-47,814; p<0.01). PBMC from aBD produced more O2– when exposed to aBD plasma (39,208/9,656-315,306) compared to HC plasma (10,135/3,394-41,873; p=0.046) or non-stimulated (10,052/3,262-37,352; p=0.028). The same occurred with HC PBMC: 24,531/4,931-73,813; 3,661/1,697-28,992 (p=0.03); 1,994/928-5,532, respectively (p=0.02). Finally, H2O2 production in aBD PBMC was enhanced by aBD plasma (55,223/17,186-253,194) versus HC plasma (35,193/2,081-331,239; p=0.05) versus non-stimulated (18,690/2,340-78,728; p=0.046). The same was observed with HC PBMC: aBD plasma (10,357/4,024-75,036); HC plasma (2,502/975-7,810, p=0.028). H2O2 and O2– production after microbial stimuli was equivalent for phagocytes from aBD, iBD, and HC.
Conclusion: Phagocytes from BD patients were not constitutively activated and responded normally to microbial and PMA stimuli. Plasma from patients with active BD exerted a strong stimulus for H2O2 and O2– production. These findings warrant further studies in order to identify possible metabolic pathways involved in neutrophil activation in BD.
S. F. Perazzio,
P. V. S. Pereira,
A. W. S. Souza,
L. E. C. Andrade,
« Back to 2013 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasma-of-active-behcets-disease-increases-oxidative-metabolism-profile-of-normal-and-patients-phagocytes/