{
  "id": 4683612,
  "title": "Lysosomal Dysfunction-Mediated IgG Accumulation Promotes Endothelial Senescence and Lesion Progression in Cerebral Cavernous Malformations",
  "url": "https://urgent.news/2026/08/31/lysosomal-dysfunction-mediated-igg-accumulation-promotes-endothelial",
  "topic": "science",
  "section": "Science",
  "published": "2026-08-31T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.08.29.747964v1?rss=1"
  },
  "original_language": "en",
  "account": "Lysosomal dysfunction leading to impaired IgG processing has been identified as a contributing factor to endothelial senescence and lesion progression in cerebral cavernous malformations (CCMs). This discovery was made through multi-omic profiling, analysis of endothelial models, and the study of CCM mice. The accumulation of IgG in CCM lesions has been observed to be associated with endothelial damage, hemorrhage, and increased disease severity. CCM-associated mTOR activation, which impairs lysosomal acidification, appears to play a role in promoting the accumulation of IgG within endothelial cells. IgG subsequently triggers the activation of NF-kB, a pathway known to induce endothelial senescence. In vivo experiments demonstrated that depleting plasma cells producing BCMA (a protein associated with CCM) helped to reduce lesion progression, while supplementation with IgG partially restored the severity of the disease. Additionally, treatment with anti-CD38, a molecule that targets IgG, was found to decrease IgG accumulation, endothelial senescence, hemorrhage, and lesion progression. These findings suggest that targeting the plasma cell-IgG axis could be a potential therapeutic strategy for treating CCMs.",
  "summary": "Endothelial senescence is increasingly recognized as a driver of vascular pathology, while immunoglobulin G (IgG) has recently been reported to accumulate in aging tissues and induce senescence in macrophages and microglia. In cerebral cavernous malformations (CCMs), IgG accumulation has been obviously observed in CCM lesions, but the contribution of IgG to endothelial injury remains unclear.…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}