It was a hard sell.
It is now accepted that the likely etiology of DDD & C3GN in older patients is a monoclonal gammopathy. And targeted treatment is treatment of choice.

But back in 2008-2009 no one would buy it. This is the very first report. #NephJC

doi.org/10.1053/j.ajkd…

Nephrology Journal Club Here is a better picture #NephJC

Didn’t have time⌚ to read the full article 📄 ? Go over this 💥 high-yield 💥 summary by Anvitha Rangan & Stephanie Torres M.D.
👉 nephjc.com/news/apoe-in-c…
#NephJC

Check out this 🤩 AMAZING 🤩 visual abstract by Jasmine Sethi
nephjc.com/news/2024/4/22…
#nephjc

🤔 Do you remember Jean Berger from our last #NephJC ? He and electron 🔬 expert, Pierre Galle, published 📃 1st description of DDD in 1962.

Read more about C3 glomerulopathy here: sciencedirect.com/science/articl…

Berger and Galle described the appearance as dark, ribbon-like, electron-dense material in the central layer (lamina densa) of the glomerular basement membrane (GBM). #NephJC

Urmila Anandh As per this seminal paper by Thomas et al., doi.org/10.1016/j.semn…, deposits can be seen in mesangium and Bownmann's capsule as well in DDD!
May be pathology experts may help out here!

T0f: C3G is mainly caused by dysregulation in the complement cascade, this can be from genetic 🧬 and/or acquired 🧪 factors.
More than 90% of C3G cases are caused by dysregulation in the alternative complement cascade, while 10% are in the classical/lectin pathways. #NephJC

T1e: Proteins & peptides’ intensity based absolute quantification (iBAQ) values were compared between the two groups to calculate fold-change and P values. #NephJC

T1f: Various other analyses performed included - immunohistochemical (IHC) staining for ApoE, and IF confocal staining for co-localization analysis. #NephJC

T1g: In traditional IF, antibodies labeled with fluorescent dyes bind to specific target proteins within the tissue sample. Confocal microscopy🔬 is a powerful imaging technique that allows for high-resolution, three-dimensional imaging of fluorescently labeled samples. #NephJC

T1h: Confocal microscopy produces clear images with improved resolution compared to traditional IF 🔬. Combining the techniques enables researchers to study the localization & expression patterns of specific proteins within tissue samples with exceptional detail. #NephJC

T2b: ⚡️ApoE⚡️
♦️DDD 🆚 controls: ~32 fold ⬆️
♦️C3GN 🆚 controls: ~5 fold ⬆️
♦️DDD 🆚 C3GN: ~9 fold ⬆️
#NephJC

T3b: Why do those differences in the DDD deposits exist? 🤔
❇️ Osmium dependent suggesting lipid component
❇️ Apo E major constituent on dense deposits

#NephJC

Curiously fats also produce various complement factors! #NephJC

⭐️Discussion⭐️
T3a: ApoE is a protein involved in the metabolism of fats.
It has been implicated in:
🧠 Alzheimer’s disease
🫀 CVD
👁️ Macular degeneration

In the 🫘 has been detected in fibrillary, immunotactoid GN, monoclonal Ig deposition disease (and, now in DDD!)
#NephJC

T2c: ⚡️ApoE⚡️🆚 other diseases
♦️Total spectral counts (TSCs) were used showing 35 for DDD and 0-1.5 in other diseases
#NephJC

Does dense deposits deposit along the Bowman’s capsule?

T2e: Confocal microscopy 🔬 for ⚡️ApoE⚡️
✅ Purpose: confirm LCM/MS findings

♦️DDD: Bright staining along GBM, Bowman’s capsule and tubular basement membrane
♦️C3GN: Negative staining
#NephJC

T1a: 12 controls, C3GN and DDD cases used for initial analysis.
Take a look 👀 at the specifics of the C3NG and DDD cases.
Anything that stands out?🤔
#NephJC