High p16INK4a, a marker of cellular senescence, is associated with renal injury, impairment and outcome in lupus nephritis
| Autor: | Frédéric Houssiau, Caroline Bouzin, Bernard Lauwerys, Pierre Coulie, Gaëlle Tilman, Christine Galant, Farah Tamirou, Nisha Limaye, Selda Aydin |
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| Přispěvatelé: | UCL - SSS/DDUV - Institut de Duve, UCL - SSS/DDUV/GECE - Génétique cellulaire, UCL - SSS/DDUV/GEPI - Epigénétique, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service de rhumatologie |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pathology
medicine.medical_specialty Kidney Systemic disease Lupus erythematosus business.industry Autoimmune diseases Systemic Immunology Lupus nephritis Renal function medicine.disease medicine.anatomical_structure Rheumatology Fibrosis medicine Renal fibrosis Immunology and Allergy Medicine business CD8 |
| Zdroj: | RMD Open, Vol 7, Iss 3 (2021) RMD open, Vol. 7, no. 3, p. e001844 [1-5] (2021) |
| ISSN: | 2056-5933 |
| Popis: | ObjectivesBecause 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.MethodsWe enumerated the number of cells positive for p16INK4a 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 p16INK4a with renal fibrosis, CD8+ T cell infiltration, systemic disease and renal function at baseline and at 5 years.ResultsThe presence of p16INK4a-positive cells was significantly associated with lower estimated glomerular filtration rate at baseline and 5 years post-treatment, independently of patient demographics and systemic disease parameters. It was also associated with higher baseline renal fibrosis and CD8+ T cell infiltration. Interestingly, we observed marked spatial co-distribution of glomerular p16INK4a-positive cells with CD8+ T cells.ConclusionWe demonstrate, for the first time, that LN biopsies characterised by renal impairment display increased p16INK4a-positive cells, associated with higher fibrosis and CD8+ T cell infiltration. Cellular senescence may represent a kidney-intrinsic disease mechanism and potentially, a novel therapeutic target in LN. |
| Databáze: | OpenAIRE |
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