Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus nephritis in mice.
Immunobiology
; 221(6): 701-8, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-26307001
ABSTRACT
Systemic lupus erythematosus is an autoimmune disease that manifests in widespread complement activation and deposition of complement fragments in the kidney. The complement pathway is believed to play a significant role in the pathogenesis and in the development of lupus nephritis. Complement factor B is an important activator of the alternative complement pathway and increasing evidence supports reducing factor B as a potential novel therapy to lupus nephritis. Here we investigated whether pharmacological reduction of factor B expression using antisense oligonucleotides could be an effective approach for the treatment of lupus nephritis. We identified potent and well tolerated factor B antisense oligonucleotides that resulted in significant reductions in hepatic and plasma factor B levels when administered to normal mice. To test the effects of factor B antisense oligonucleotides on lupus nephritis, we used two different mouse models, NZB/W F1 and MRL/lpr mice, that exhibit lupus nephritis like renal pathology. Antisense oligonucleotides mediated reductions in circulating factor B levels were associated with significant improvements in renal pathology, reduced glomerular C3 deposition and proteinuria, and improved survival. These data support the strategy of using factor B antisense oligonucleotides for treatment of lupus nephritis in humans.
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Base de dados:
MEDLINE
Assunto principal:
Nefrite Lúpica
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Fator B do Complemento
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Oligonucleotídeos Antissenso
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Hepatócitos
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Rim
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Lúpus Eritematoso Sistêmico
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Complexo Antígeno-Anticorpo
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article