RESUMEN
Diagnostic accuracy of anti-DNase I antibodies measurement in a differentiation between SLE and other autoimmune rheumatic diseases was evaluated. The share of anti-DNase I and actin in the DNase I activity decrease in SLE was established. Serum samples were obtained from 54 patients with verified SLE, 52 control patients with other autoimmune rheumatic diseases, and 44 healthy persons. Anti-DNase I concentrations were measured by ELISA. Free and actin inhibited DNase I activities were evaluated in the fresh serum samples. The appraisal of antibodies and actin effects on DNase I activity was made using multiple regression. Anti-DNase I antibodies were positive in 35 SLE and 8 control patients, without significant difference between the mean antibody concentrations. Sensitivity of this test was 64.81 %, and specificity-84.62 %. Mean free DNase I activity in SLE was somewhat lower than in the control group as a result of augmented frequency of extremely low enzyme activities. On the contrary, after the exclusion of the latter cases we have revealed elevated mean free DNase I activity in the other SLE patients comparing to the similar control subgroup. Unlike the controls, low serum DNase I activity in SLE arose not only from actin and antibody action, but also, in half of the cases, from unidentified factor, related to active SLE. The accuracy of the anti-DNase I antibodies measurement is approximate to the present reference standard of SLE diagnostics. We first demonstrated that neither antibodies nor actin caused DNase I activity decrease in SLE.
Asunto(s)
Autoanticuerpos/sangre , Desoxirribonucleasa I/inmunología , Lupus Eritematoso Sistémico/inmunología , Actinas/sangre , Área Bajo la Curva , Biomarcadores/sangre , Estudios de Casos y Controles , Desoxirribonucleasa I/antagonistas & inhibidores , Ensayo de Inmunoadsorción Enzimática , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/enzimología , Valor Predictivo de las Pruebas , Curva ROC , Análisis de Regresión , Reproducibilidad de los ResultadosRESUMEN
The objective of this research was to adapt the experimental model simulating the nucleoprotein disposal disorders in systemic lupus erythematosus (SLE) for further study of its extracorporeal correction, as well as to assess validity of the model by short-term experiment. Twenty to female Wistar rats were intraperitoneally injected with the chromatin-containing extract from bovine liver followed by intravenous administration of anti-DNA antibodies derived from SLE patients. After these procedures plasma concentrations of anti-dsDNA, circulating immune complexes and DNA became sharply increased, together with distinct elevation of leukocytes. On the contrary, changes in erythrocytes, platelets, total protein concentration, creatinine, asparagine and alanine aminotransferase activities, as well as blood coagulation time were changed insignificantly. Using direct immunofluorescence of cryosections, we detected human IgG deposition in rat kidneys treated in accordance with the simulation protocol. Thus, our model reproduces essential DNA disposal disorders in SLE without any animal death or the life-threatening changes in examined markers during short-term experiment.
Asunto(s)
Anticuerpos Antinucleares/sangre , Complejo Antígeno-Anticuerpo/sangre , ADN/sangre , Inmunoglobulina G/sangre , Lupus Eritematoso Sistémico/sangre , Nucleoproteínas/sangre , Alanina Transaminasa/sangre , Animales , Plaquetas/inmunología , Plaquetas/patología , Bovinos , Mezclas Complejas/administración & dosificación , Mezclas Complejas/inmunología , Creatinina/sangre , ADN/inmunología , Modelos Animales de Enfermedad , Eritrocitos/inmunología , Eritrocitos/patología , Femenino , Humanos , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Riñón/química , Riñón/inmunología , Riñón/patología , Hígado/química , Hígado/inmunología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Nucleoproteínas/inmunología , Ratas , Ratas Wistar , Transaminasas/sangreRESUMEN
Efficacy and safety of the extracorporeal blood perfusion through DNase I- and C1q-containing magnetic beads have been evaluated using the experimental model simulating the nucleoprotein disposal disorders in systemic lupus erythematosus (SLE). The study was performed using 20 rats in which the essential impairments of nucleoprotein catabolism typical for SLE were modeled. The animals were randomized into the experimental group and the placebo perfusion control group. Rats of the experimental group were characterized by the statistically significant reduction of increased levels of circulating immune complexes and plasma DNA as well as diminished levels of plasma creatinine and kidney IgG deposition as compared with placebo controls. During short-term experiment there were neither animal deaths nor substantial blood cell destruction and hepatotoxicity signs.