A novel pseudovirus encoding Diphtheriatoxin A fragment eliminates autoantibody-producing B cells and inhibits lupus in the BWF1 mouse model.
Lupus-associated anti-dsDNA Abs plays an important role in the triggering and development of human systemic lupus erythematosus (SLE). The method of targeting B cells that produce anti-dsDNA Abs has become a promising way to treat autoantibody-mediated SLE in the immunotherapy field. In this study, we reported a novel pseudovirus, which consisted of the peptide DWEYSVWLSN and a plasmid encoding the Diphtheriatoxin A fragment (DTA). Our data demonstrated that vaccination of lupus-prone (BWF1) mice with the pseudovirus could eliminate anti-dsDNA antibody-producing B cells, reduce serum anti-dsDNA antibody levels, impede the development of proteinuria and improve survival. These findings suggested that this novel pseudovirus ablated autoreactive B cells and might represent a promising therapeutic strategy for autoantibody-mediated diseases.
Tan
Hu
H
Department of Cardiovascular Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
Yang
Xuemei
X
Cui
Shehuai
S
Yang
Zhao
Z
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D002470:Cell Survival; D004167:Diphtheria Toxin / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011507:Proteinuria / Q000276:immunology; D016019:Survival Analysis; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014780:Viruses / Q000235:genetics / Q000276:immunology / Q000648:ultrastructure
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D004167:Diphtheria Toxin; D010446:Peptide Fragments; D014765:Viral Vaccines; C029795:diphtheria toxin fragment A