The DNA co-vaccination using Sm antigen and IL-10 as prophylactic experimental therapy ameliorates nephritis in a model of lupus induced by pristane

• Published in: PloS one Vol. 16; no. 10; p. e0259114
• Main Authors: Martín-Márquez, Beatriz Teresita, Satoh, Minoru, Hernández-Pando, Rogelio, Martínez-García, Erika Aurora, Petri, Marcelo Heron, Sandoval-García, Flavio, Pizano-Martinez, Oscar, García-Iglesias, Trinidad, Corona-Meraz, Fernanda Isadora, Vázquez-Del Mercado, Monica
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27-10-2021; Public Library of Science (PLoS)
• Subjects: Analysis; Animal models; Animals; Antibodies; Antigenic determinants; Antigens; Autoantibodies; Autoantibodies - immunology; Autoantigens - immunology; Autoimmune diseases; Biology and Life Sciences; Chronic conditions; Cloning; Cytokines; Damage; Deoxyribonucleic acid; DNA; DNA vaccines; Electron microscopy; Endotoxins; Enzyme-linked immunosorbent assay; Epitopes; Evaluation; Female; Genetic aspects; Immunization; Immunofluorescence; Immunoglobulin G; Immunological tolerance; Immunoprecipitation; Interleukin 10; Interleukin-10 - administration & dosage; Interleukin-10 - pharmacology; Isotypes; Kidneys; Lupus; Lupus Erythematosus, Systemic - prevention & control; Lupus nephritis; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Nephritis; Polypeptides; Pristane; Properties; Proteinuria; Research and Analysis Methods; Splenocytes; Systemic lupus erythematosus; Therapeutics, Experimental; Therapies, Investigational; Vaccination; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - pharmacology; γ-Interferon; Mexico; Cuba
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0259114

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.
The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D183-119, D2, B´/B, and B´/BCOOH in co-vaccination with IFN-γ or IL-10 in a murine model of lupus induced by pristane.
To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D183-119, D2, B´/B, B´/BCOOH, 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 35S 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.
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).
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.