Your browser doesn't support javascript.
loading
Myeloperoxidase Peptide-Based Nasal Tolerance in Experimental ANCA-Associated GN.
Gan, Poh-Yi; Tan, Diana S Y; Ooi, Joshua D; Alikhan, Maliha A; Kitching, A Richard; Holdsworth, Stephen R.
Afiliación
  • Gan PY; Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; and.
  • Tan DS; Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; and.
  • Ooi JD; Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; and.
  • Alikhan MA; Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; and.
  • Kitching AR; Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; and Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
  • Holdsworth SR; Centre for Inflammatory Diseases, Department of Medicine, Monash University, Clayton, Victoria, Australia; and Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia Stephen.holdsworth@monash.edu.
J Am Soc Nephrol ; 27(2): 385-91, 2016 Feb.
Article en En | MEDLINE | ID: mdl-26047792
Less toxic treatment options for patients with myeloperoxidase (MPO)-ANCA-associated GN are needed. Using an established murine model of focal necrotizing GN mediated by autoimmunity to MPO (autoimmune anti-MPO GN), we assessed the capacity for nasal tolerance induced by nasal insufflation of the immunodominant nephritogenic MPO peptide (MPO409-428) to attenuate this disease. Compared with mice that received an irrelevant immunodominant ovalbumin (OVA) peptide, OVA323-339, mice that received MPO409-428 were protected from the development of humoral and cell-mediated autoimmunity to full-length MPO and the development of GN. In mice with established anti-MPO autoimmunity, nasal insufflation of MPO409-428 as a therapeutic attenuated anti-MPO GN. To investigate the nature of this induced tolerance, we isolated CD4(+) T cells from the upper airway draining lymph nodes of both OVA323-339- and MPO409-428-tolerized mice. Adoptive transfer of CD4(+) T cells from MPO409-428- but not OVA323-339-tolerized mice to animals with established anti-MPO autoimmunity attenuated the subsequent development of GN, confirming that the immunosuppression induced by these T cells is antigen specific. Ex vivo studies showed that nasal tolerance to MPO is mediated by both conventional and induced T regulatory cells. The strong homology between the pathogenic human MPO B cell epitope recognized by ANCA in patients with acute vasculitis and the nephritogenic murine T cell MPO epitope emphasizes the clinical relevance of this study.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nariz / Peroxidasa / Anticuerpos Anticitoplasma de Neutrófilos / Glomerulonefritis / Tolerancia Inmunológica Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nariz / Peroxidasa / Anticuerpos Anticitoplasma de Neutrófilos / Glomerulonefritis / Tolerancia Inmunológica Tipo de estudio: Risk_factors_studies Límite: Animals Idioma: En Revista: J Am Soc Nephrol Asunto de la revista: NEFROLOGIA Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos