{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:09:43Z","timestamp":1790222983112,"version":"4.1.0"},"reference-count":20,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"unspecified","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Actions de Recherche Concert\u00e9es, UCLouvain","award":["ARC 19\/24-098"],"award-info":[{"award-number":["ARC 19\/24-098"]}]},{"name":"Fonds de la Recherche Fondamentale Strat\u00e9gique-WELBIO","award":["WELBIO-CR-2019A-03R"],"award-info":[{"award-number":["WELBIO-CR-2019A-03R"]}]},{"name":"F.R.S.-F.N.R.S."}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2021,10,5]]},"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Because a significant fraction of patients with lupus nephritis (LN) develops renal impairment, there is a need to better understand the mechanisms underlying disease progression. Here, we assessed for cellular senescence in the LN kidney, and its association with disease severity and outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We enumerated the number of cells positive for p16<jats:sup>INK4a<\/jats:sup> protein, a marker of cellular senescence, by immunohistochemistry followed by digital quantification, on renal biopsies from 40 patients with active LN. We tested for an association of p16<jats:sup>INK4a<\/jats:sup> with renal fibrosis, CD8<jats:sup>+<\/jats:sup> T cell infiltration, systemic disease and renal function at baseline and at 5\u2009years.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The presence of p16<jats:sup>INK4a<\/jats:sup>-positive cells was significantly associated with lower estimated glomerular filtration rate at baseline and 5\u2009years post-treatment, independently of patient demographics and systemic disease parameters. It was also associated with higher baseline renal fibrosis and CD8<jats:sup>+<\/jats:sup> T cell infiltration. Interestingly, we observed marked spatial co-distribution of glomerular p16<jats:sup>INK4a<\/jats:sup>-positive cells with CD8<jats:sup>+<\/jats:sup> T cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We demonstrate, for the first time, that LN biopsies characterised by renal impairment display increased p16<jats:sup>INK4a<\/jats:sup>-positive cells, associated with higher fibrosis and CD8<jats:sup>+<\/jats:sup> T cell infiltration. Cellular senescence may represent a kidney-intrinsic disease mechanism and potentially, a novel therapeutic target in LN.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2021-001844","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T10:51:34Z","timestamp":1634899894000},"page":"e001844","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["High p16<sup>INK4a<\/sup>, a marker of cellular senescence, is associated with renal injury, impairment and outcome in lupus nephritis"],"prefix":"10.1136","volume":"7","author":[{"given":"Ga\u00eblle","family":"Tilman","sequence":"first","affiliation":[{"name":"Genetics of Autoimmune Diseases and Cancer, de Duve Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium"},{"name":"Department of Rheumatology, Cliniques universitaires Saint-Luc, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Bouzin","sequence":"additional","affiliation":[{"name":"IREC Imaging Platform (2IP), Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selda","family":"Aydin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Tamirou","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Cliniques universitaires Saint-Luc, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Galant","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre G","family":"Coulie","sequence":"additional","affiliation":[{"name":"de Duve Institute, Universit\u00e9 catholique de Louvain, Brussels, Belgium"},{"name":"Walloon Excellence in Life Sciences and Biotechnology, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Houssiau","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Cliniques universitaires Saint-Luc, Brussels, Belgium"},{"name":"P\u00f4le de pathologies rhumatismales syst\u00e9miques et inflammatoires, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Lauwerys","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Cliniques universitaires Saint-Luc, Brussels, Belgium"},{"name":"P\u00f4le de pathologies rhumatismales syst\u00e9miques et inflammatoires, Institut de Recherche Exp\u00e9rimentale et Clinique, Universit\u00e9 catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9820-4794","authenticated-orcid":false,"given":"Nisha","family":"Limaye","sequence":"additional","affiliation":[{"name":"Genetics of Autoimmune Diseases and Cancer, de Duve Institute, Universit\u00e9 catholique de Louvain, Brussels, 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