Open AccessThe DNA co-vaccination using Sm antigen and IL-10 as prophylactic experimental therapy ameliorates nephritis in a model of lupus induced by pristane
Author(s) -
Beatriz Teresita Martín-Márquez,
Minoru Satoh,
Rogelio Hernández-Pando,
Erika Aurora Martínez-García,
Marcelo H. Petri,
Flavio Sandoval-García,
Óscar Pizano-Martínez,
Trinidad GarcíaIglesias,
Fernanda-Isadora Corona-Meraz,
Mónica Vázquez-Del Mercado
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0259114
Subject(s) - systemic lupus erythematosus , lupus nephritis , autoantibody , immunology , pristane , antigen , antibody , medicine , epitope , immunofluorescence , chemistry , pathology , disease , hydrocarbon , organic chemistry
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-γ 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-γ, 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 35 S and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-γ 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.