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Dual Costimulatory and Coinhibitory Targeting with a Hybrid Fusion Protein as an Immunomodulatory Therapy in Lupus Nephritis Mice Models.
Guiteras, Jordi; Crespo, Elena; Fontova, Pere; Bolaños, Nuria; Gomà, Montse; Castaño, Esther; Bestard, Oriol; Grinyó, Josep M; Torras, Joan.
Afiliação
  • Guiteras J; Experimental Nephrology Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
  • Crespo E; Fundació Bosch i Gimpera, University of Barcelona, 08028 Barcelona, Spain.
  • Fontova P; Experimental Nephrology and Renal Transplantation Laboratory, Nephrology Department, Vall d'Hebrón University Hospital, 08035 Barcelona, Spain.
  • Bolaños N; Experimental Nephrology Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
  • Gomà M; Experimental Nephrology and Renal Transplantation Laboratory, Nephrology Department, Vall d'Hebrón University Hospital, 08035 Barcelona, Spain.
  • Castaño E; Pathology Department, Bellvitge University Hospital, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
  • Bestard O; Centres Científics i Tecnològics, L'Hospitalet de Llobregat, University of Barcelona, 08907 Barcelona, Spain.
  • Grinyó JM; Experimental Nephrology and Renal Transplantation Laboratory, Nephrology Department, Vall d'Hebrón University Hospital, 08035 Barcelona, Spain.
  • Torras J; Faculty of Medicine, Bellvitge Campus, L'Hospitalet de Llobregat, University of Barcelona, 08907 Barcelona, Spain.
Int J Mol Sci ; 23(15)2022 Jul 29.
Article em En | MEDLINE | ID: mdl-35955542
ABSTRACT
Systemic lupus erythematosus is a complex autoimmune disorder mostly mediated by B-cells in which costimulatory signals are involved. This immune dysregulation can cause tissue damage and inflammation of the kidney, resulting in lupus nephritis and chronic renal failure. Given the previous experience reported with CTLA4-Ig as well as recent understanding of the PD-1 pathway in this setting, our group was encouraged to evaluate, in the NZBWF1 model, a human fusion recombinant protein (Hybri) with two domains CTLA4, blocking the CD28-CD80 costimulatory pathway, and PD-L2, exacerbating the PD-1-PD-L2 coinhibitory pathway. After achieving good results in this model, we decided to validate the therapeutic effect of Hybri in the more severe MRL/lpr model of lupus nephritis. The intraperitoneal administration of Hybri prevented the progression of proteinuria and anti-dsDNA antibodies to levels like those of cyclophosphamide and reduced the histological score, infiltration of B-cells, T-cells, and macrophages and immune deposition in both lupus-prone models. Additionally, Hybri treatment produced changes in both inflammatory-related circulating cytokines and kidney gene expression. To summarize, both in vivo studies revealed that the Hybri effect on costimulatory-coinhibitory pathways may effectively mitigate lupus nephritis, with potential for use as a maintenance therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nefrite Lúpica / Lúpus Eritematoso Sistêmico Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nefrite Lúpica / Lúpus Eritematoso Sistêmico Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Espanha
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