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http://hdl.handle.net/2445/151537
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DC Field | Value | Language |
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dc.contributor.author | Luque Gómez, Ana | - |
dc.contributor.author | Serrano, Inmaculada | - |
dc.contributor.author | Ripoll Llagostera, Èlia | - |
dc.contributor.author | Malta, Catarina | - |
dc.contributor.author | Gomà, Montse | - |
dc.contributor.author | Blom, Anna M. | - |
dc.contributor.author | Grinyó Boira, Josep M. | - |
dc.contributor.author | Rodríguez de Córdoba, Santiago | - |
dc.contributor.author | Torras Ambròs, Joan | - |
dc.contributor.author | Aran Perramon, Josep M. | - |
dc.date.accessioned | 2020-03-01T13:20:35Z | - |
dc.date.available | 2020-11-06T06:10:22Z | - |
dc.date.issued | 2019-11-06 | - |
dc.identifier.uri | http://hdl.handle.net/2445/151537 | - |
dc.description.abstract | Lupus nephritis (LN) is a chronic autoimmune-inflammatory condition that can lead to end-stage renal disease because of the breakage of immune self-tolerance occurring in systemic lupus erythematosus (SLE) patients. Presently available immunosuppressive treatments for LN are suboptimal and can induce significant side effects. We have recently characterized a novel immunomodulatory activity on the minor isoform of the classical pathway complement inhibitor, C4BP(b-). We show here that C4BP(b-) treatment prevented the development of proteinuria and albuminuria, decreased significantly the formation of anti-dsDNA antibodies and, locally, mitigated renal glomerular IgG and C3 deposition and generation of apoptotic cells, with the consequent histological improvement and increased survival in lupus-prone mice. The therapeutic efficacy of C4BP(b-) was analogous to that of the broad-acting immunosuppressant cyclophosphamide (CYP). Remarkably, a comparative transcriptional profiling analysis revealed that: 1) the renal gene expression signature resulting from C4BP(b-) treatment turned out to be 10 times smaller than that induced by CYP treatment, and 2) C4BP(b-) immunomodulation induced significant downregulation of LN relevant transcripts indicating immunopathogenic cell infiltration, including activated T cells (Lat), B cells (Cd19, Ms4a1, Tnfrsf13c), inflammatory phagocytes (Irf7) and neutrophils (Prtn3, S100a8, S100a9). Furthermore, cytokine profiling and immunohistochemistry confirmed that C4BP(b-), through systemic and local CXCL13 downregulation, was able to prevent ectopic lymphoid structures neogenesis in aged LN mice. Thus, because of its anti-inflammatory and immunomodulatory activities and high specificity, C4BP(b-) could be considered for further clinical development in SLE patients. | ca |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | ca |
dc.publisher | Elsevier BV | ca |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1016/j.kint.2019.10.016 | - |
dc.relation.ispartof | Kidney International, 2020, vol. 97, issue. 3, p. 551-566 | - |
dc.relation.uri | https://doi.org/10.1016/j.kint.2019.10.016 | - |
dc.rights | cc by-nc-nd (c) International Society of Nephrology, 2019 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Malalties del ronyó | - |
dc.subject.classification | Malalties autoimmunitàries | - |
dc.subject.other | Kidney diseases | - |
dc.subject.other | Autoimmune diseases | - |
dc.title | Non-canonical immunomodulatory activity of complement regulator C4BP(β-) limits the development of lupus nephritis | ca |
dc.type | info:eu-repo/semantics/article | ca |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.date.updated | 2020-02-23T19:13:12Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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KI PAPER (Lupus) (Luque et al.) (IDIBELL Repository).pdf | 8.01 MB | Adobe PDF | View/Open |
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