The DNA co-vaccination using Sm antigen and IL-10 as prophylactic experimental therapy ameliorates nephritis in a model of lupus induced by pristane
Abstract
Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1((83-119),) D2, and B/B epitopes. Objectives The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D1(83-119), D2, B/B, and B/B-COOH in co-vaccination with IFN-gamma or IL-10 in a murine model of lupus induced by pristane. Material and methods To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D1(83-119), D2, B'/B, B'/B-COOH, IFN-gamma, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with S-35 and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-gamma from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy. Results The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048). Conclusion The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy.
Más información
Título según WOS: | ID WOS:000755636500048 Not found in local WOS DB |
Título de la Revista: | PLOS ONE |
Volumen: | 16 |
Número: | 10 |
Editorial: | PUBLIC LIBRARY SCIENCE |
Fecha de publicación: | 2021 |
DOI: |
10.1371/journal.pone.0259114 |
Notas: | ISI |