Identification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone loss

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-10-05T16:33:38Z
Fecha de publicación2016-01-01
ResumenObjectives Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) appear before disease onset and are associated with bone destruction. We aimed to dissect the role of ACPAs in osteoclast (OC) activation and to identify key cellular mediators in this process. Methods Polyclonal ACPA were isolated from the synovial fluid (SF) and peripheral blood of patients with RA. Monoclonal ACPAs were isolated from single SF B-cells of patients with RA. OCs were developed from blood cell precursors with or without ACPAs. We analysed expression of citrullinated targets and peptidylarginine deiminases (PAD) enzymes by immunohistochemistry and cell supernatants by cytometric bead array. The effect of an anti-interleukin (IL)-8 neutralising antibody and a pan-PAD inhibitor was tested in the OC cultures. Monoclonal ACPAs were injected into mice and bone structure was analysed by micro-CT before and after CXCR1/2 blocking with reparixin. Results Protein citrullination by PADs is essential for OC differentiation. Polyclonal ACPAs enhance OC differentiation through a PAD-dependent IL-8-mediated autocrine loop that is completely abolished by IL-8 neutralisation. Some, but not all, human monoclonal ACPAs derived from single SF B-cells of patients with RA and exhibiting distinct epitope specificities promote OC differentiation in cell cultures. Transfer of the monoclonal ACPAs into mice induced bone loss that was completely reversed by the IL-8 antagonist reparixin. Conclusions We provide novel insights into the key role of citrullination and PAD enzymes during OC differentiation and ACPA-induced OC activation. Our findings suggest that IL8-dependent OC activation may constitute an early event in the initiation of the joint specific inflammation in ACPA-positive RA.es_ES
Doihttps://doi.org/10.1136/annrheumdis-2015-208093es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/5438
Idiomaenes_ES
EditorialBMJ PUBLISHING GROUPes_ES
RelaciónAnnals of the Rheumatic Diseaseses_ES
URL relacionadohttps://doi.org/10.1136/annrheumdis-2015-208093es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteAnnals of the Rheumatic Diseases
TítuloIdentification of a novel chemokine-dependent molecular mechanism underlying rheumatoid arthritis-associated autoantibody-mediated bone losses_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorKrishnamurthy, Akilan
AutorJoshua, Vijay
AutorHensvold, Aase Haj
AutorJin, Tao
AutorSun, Meng
AutorVivar, Nancy
AutorYtterberg, A. Jimmy
AutorEngstrom, Marianne
AutorFernandes-Cerqueira, Catia
AutorAmara, Khaled
AutorMagnusson, Malin
AutorWigerblad, Gustaf
AutorKato, Jungo
AutorJimenez-Andrade, Juan Miguel
AutorTyson, Kerry
AutorRapecki, Stephen
AutorLundberg, Karin
AutorCatrina, Sergiu-Bogdan
AutorJakobsson, Per-Johan
AutorSvensson, Camilla
AutorMalmstrom, Vivianne
AutorKlareskog, Lars
AutorWahamaa, Heidi
AutorCatrina, Anca I.
AutorKrishnamurthy, Akilanes_ES
AutorJoshua, Vijayes_ES
AutorHensvold, Aase Hajes_ES
AutorJin, Taoes_ES
AutorSun, Menges_ES
AutorVivar, Nancyes_ES
AutorYtterberg, A. Jimmyes_ES
AutorEngstrom, Mariannees_ES
AutorFernandes-Cerqueira, Catiaes_ES
AutorAmara, Khaledes_ES
AutorMagnusson, Malines_ES
AutorWigerblad, Gustafes_ES
AutorKato, Jungoes_ES
AutorJimenez-Andrade, Juan Migueles_ES
AutorTyson, Kerryes_ES
AutorRapecki, Stephenes_ES
AutorLundberg, Karines_ES
AutorCatrina, Sergiu-Bogdanes_ES
AutorJakobsson, Per-Johanes_ES
AutorSvensson, Camillaes_ES
AutorMalmstrom, Viviannees_ES
AutorKlareskog, Larses_ES
AutorWahamaa, Heidies_ES
AutorCatrina, Anca I.es_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
Número4es_ES
Rango de páginas721-729es_ES
URL relacionadahttps://doi.org/10.1136/annrheumdis-2015-208093
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen75es_ES

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