Background Ceruloplasmin is an oxidoreductase considered to be a key intracellular antioxidant factor that substantially contributes in SLE pathogenesis. There is disequilibrium between ROS production and disposal in SLE shifted to accumulation of toxic products of the free radical reactions. The origin of such imbalance still remains unclear. Production of autoantibodies to ceruloplasmin and other antioxidant enzymes could be putative source of their dysfunction.
Purpose Assessment of interrelations between oxidase activity of ceruloplasmin, anti-ceruloplasmin antibodies presence and basic clinical and laboratory parameters of SLE with the use of ceruloplasmin immobilized on the magnetic beads.
Methods The research was conducted according to the WMA Helsinki Declaration after approval of the local ethics committee. 63 SLE patients were included in the research when admitted to rheumatology unit of Volgograd Municipal Hospital of Emergency Care #25. The diagnosis was verified using EULAR/ACR classification criteria (2019). Serum samples were collected after inclusion as well as before the discharge. Disease activity was assessed by means of ECLAM index. 30 healthy volunteers were included in the reference group. Anti-ceruloplasmin antibodies were detected by ELISA using ceruloplasmin coated magnetic polyacrylamide beads that have been made by original technology. Oxidase ceruloplasmin activity was measured using paraphenylenediamine oxidation technique. The values were expressed as optical density units (ODU). Results were expressed as means ± standard deviations.
Results Mean ECLAM index in SLE group was 10.2±6.7 points. Mean anti-ceruloplasmin antibody value in the reference group was 0.020±0.014 ODU. None of individual values was outside reference interval (M+3SD) meaning that there were no antibody positive cases in the reference group. 30 (47.6%) SLE patients were demonstrated serum anti-ceruloplasmin antibodies, and its mean concentration was 0.134±0.026 ODU. Ceruloplasmin activity in anti-ceruloplasmin antibody positive SLE patients was significantly lower than in antibody negative patients (1.234±0.315 ODU and 1.822±0.154 ODU, respectively, p<0.001). SLE activity positively correlated with anti-ceruloplasmin antibody concentration in contrast to its negative correlation with ceruloplasmin activity. Moderate but significant increase of ceruloplasmin activity and decrease of the antibody concentration were found after in-hospital treatment.
Conclusion Anti-ceruloplasmin antibodies, which can be found in a large proportion of SLE patients, are eventual inhibitors of ceruloplasmin oxidase activity, thereby leading to insufficiency of the extracellular portion of the antioxidant system. The study of antibody formation to ceruloplasmin, as well as its enzymatic activity, expands the existing understanding of SLE pathogenesis and outlines ways for further research in the field of immunological considerations of antioxidant system.
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