Adenosine deaminase enzyme activity is increased and negatively correlates with catalase, superoxide dismutase and glutathione peroxidase in patients with Behçet's disease: original contributions/clinical and laboratory investigations.
OBJECTIVE
Behçet's disease (BD) is an inflammatory vasculitis with immunologic, endothelial and neutrophil alterations. Adenosine deaminase (AD) is a marker of T-cell activation and is related to the production of reactive oxygen species by neutrophils with the production of NO(*), O(2)(*-), H(2)O(2) and OH(*). We reported increased tumour necrosis factor-alpha, soluble interleukin-2 receptor, interleukin-6, interleukin-8 and NO(*) in active BD. As there is a relation between cytokines, T cells and oxidative stress in inflammatory diseases, this study further evaluated: (1) plasma AD activity and its correlation with acute phase reactants; (2) thiobarbituric acid-reactive substances (TBARS) as an indicator for lipid peroxidation; and (3) antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase in patients with BD. The effect of disease activity and correlations between the measured parameters were explored.


METHODS
A total of 35 active (n=17) or inactive (n=18) patients with BD (16 men, 19 women) satisfying International Study Group criteria, and 20 age-matched and sex-matched controls (nine men, 11 women) were included in this cross-sectional case-control study. AD and TBARS were measured in plasma, catalase in red blood cells (RBC), and SOD and GSHPx in both plasma and RBC in both groups. Acute phase reactants (alpha(1)-antitrypsin, alpha(2)-macroglobulin, neutrophils, erythrocyte sedimentation rate) were used to classify patients as active or inactive.


RESULTS
Plasma AD (mean+/-standard error of the mean, 36.1+/-0.7 U/l) and TBARS (4.2+/-0.1 nmol/ml) levels were significantly (for each, p<0.001) higher in BD than in controls (24.1+/-0.8 U/l and 1.6+/-0.1 nmol/ml, respectively). RBC catalase activity was significantly (p<0.001) lower in BD than in controls (120.9+/-3.8 versus 160.3+/-4.1 k/g haemoglobin). SOD and GSHPx activities were significantly lower in both plasma and erythrocytes of patients with BD than in controls (plasma SOD, 442.4+/-8.6 versus 636.4+/-9.2 U/ml, p<0.001; RBC SOD, 3719.2+/-66.0 versus 4849.7+/-49.0 U/g haemoglobin, p<0.001; plasma GSHPx, 73.1+/-1.5 versus 90.6+/-2.9 U/ml, p<0.001; RBC GSHPx, 600.7+/-8.0 versus 670.6+/-10.1 U/g haemoglobin, p<0.001). Active BD patients had significantly lower antioxidant enzymes (except RBC catalase) and higher AD and TBARS levels than inactive subjects (for each, p<0.01). When considering all BD patients, a significant positive correlation was present between AD and TBARS (p<0.001) whereas both AD and TBARS were negatively correlated with antioxidant enzymes (for each, p<0.05).


CONCLUSIONS
AD and lipid peroxidation are increased and associated with defective antioxidants in BD, suggesting interactions between activated T cells and neutrophil hyperfunction. Measures of pro-oxidative stress and antioxidative defence with AD activity as an indicator of T-cell activation can be considered as significant supportive diagnostic indicators, especially in active disease. In addition, strengthening the antioxidant defence may contribute to treatment modalities.
Erkiliç
Kuddusi
K
Department of Ophthalmology, Erciyes University Medical Faculty, Sivas Cad, Cebeci Apt. A-Blok 175/15, TR-38020 Kayseri, Turkey.
Evereklioglu
Cem
C
Cekmen
Mustafa
M
Ozkiris
Abdullah
A
Duygulu
Fuat
F
Dogan
Hakki
H
D000209:Acute-Phase Proteins / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001528:Behcet Syndrome / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D002374:Catalase / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D013482:Superoxide Dismutase / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000209:Acute-Phase Proteins; D015415:Biomarkers; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000243:Adenosine Deaminase