Mouse and cell study: lysosomal IgG buildup linked to endothelial senescence in cerebral cavernous malformations
In this abstract, multi-omic profiling, endothelial models and CCM mice linked IgG-secreting plasma cells in lesions to endothelial senescence, hemorrhage and disease severity; impaired lysosomal IgG processing and NF-κB-dependent senescence were proposed as mechanisms. [1]
Automatic summary · not editorially reviewed
The key findings
IgG-secreting plasma cells were enriched in CCM lesions and associated with endothelial senescence, hemorrhage and disease severity. [1]
CCM loss-associated mTOR activation impaired lysosomal acidification and IgG processing, and IgG induced NF-κB-dependent endothelial senescence. [1]
In mice, plasma cell depletion attenuated lesion progression, IgG supplementation partially restored severity, and anti-CD38 reduced IgG, senescence, hemorrhage and lesions. [1]
The source at a glance
- Study type / format
- Preclinical study (abstract): multi-omic profiling, endothelial models and CCM mice
- Population / context
- Endothelial models and CCM mice, with lesion tissue profiled; no human participants reported in the abstract.
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- August 31, 2026
IgG plasma cells in CCM lesions
The abstract reports that IgG accumulation had been observed in cerebral cavernous malformation (CCM) lesions, but the contribution of IgG to endothelial injury was unclear. Using multi-omic profiling, the authors identified IgG-secreting plasma cells enriched in lesions, associated with endothelial senescence, hemorrhage and disease severity. These are described associations in the studied models, not proof that IgG causes harm in people.
Supporting source [1]
Lysosomal processing and NF-κB senescence in models
According to the abstract, CCM loss-associated mTOR activation impaired lysosomal acidification and IgG processing, promoting intracellular IgG accumulation. IgG in turn induced NF-κB-dependent endothelial senescence. These mechanistic steps come from endothelial models and CCM mice; the abstract does not report human outcome data, and the findings do not establish a treatment for people.
Supporting source [1]
Plasma cell depletion and anti-CD38 in CCM mice
In vivo, the abstract states, BCMA-mediated plasma cell depletion attenuated lesion progression, whereas IgG supplementation partially restored disease severity. Anti-CD38 treatment likewise reduced IgG accumulation, endothelial senescence, hemorrhage and lesion progression. These are experimental manipulations in mice, described in an abstract only; they are not evidence of benefit or safety in patients, and no dosing is reported.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings come from multi-omic profiling, endothelial models and CCM mice, with no human outcome data reported. Associations and experimental manipulations do not establish causation or patient benefit, and no dosing is given.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Yang Y, Sun Y, Zhao S, Zhou Q, Wang H, Sun R, Huo R, Dao L, Xu Z, Liu J, Zhai RG, Chen Y, Zhang Q, Guo Z, Ho WS, Wang J, Lu RO, Cao Y. · europepmc.org · August 31, 2026