Glomerulus(immune)

1.Glomerular immunopathologic patterns#

• IgG, IgA, IgM, κ, λ, C1q, C3
  • 其他也可染C4d(ABMR), IgG subclass(MIDD...), simian virus 40(SV40) large T antigen(BK, JC virus), EBV/CMV Ag, congo red(amyloidosis; 需要厚切(10um厚)), serum amyloid A(AA), type IV collagen的α3, α5 chains(TBMD, Alport's syndrome), type III collagen(collagenofibrotic glomerulopathy), fibronectin(fibronectin glomerulopathy), von Kossa stain(染Ca), Perls Prussian blue stain(染iron), PLA2R(MGN, 2009), THSD7A(MGN, 2014)；新抗原 EXT1/EXT2, NELL1, SEMA3B, PCDH7, HTRA1, NCAM1(各有不同臨床病理)〔PMID 36016931〕, myoglobin, lymphocyte surface Ag(lymphoma...)
• Intensity: 0~4+(有些lab只到3+); ≦1+基本上是non-specific
  • 比其他depositions≧2+則為predominant: 依 2013 C3G 共識，腎絲球以 C3 為主且強度較其他免疫反應物(IgG/A/M/C1q)高出≥2個等級即定義為 C3 glomerulopathy (DDD/C3GN)，用以與免疫複合物型 MPGN 區分〔PMID 24172683〕
  • 在fibrosis/sclerotic area較易有nonspecific deposition of IgM, C1q, C3
  • 除了glomerulus外也要看tubules, tubular BM, interstitium, BV
• Negative for immune deposits
  • Crescentic pauci-immune GN or MCD/FSGS(小心variants and 有時候有non-specific IgM, C3 deposits) or collagenofibrotic glomerulopathy or non-AL/AH/AHL forms of amyloidosis or DM nephropathy or TBMD/alport's syndrome
• Linear deposition in the capillary walls =>anti-GBM disease
  • 【線性螢光鑑別】: Anti-GBM 為強烈平滑、連續性、高強度之 IgG (偶見 C3, 罕見 IgA/IgM) 線狀螢光，可伴隨遠端腎小管基底膜沉積 (10-67%，因遠端小管亦表現 α3(IV) NC1)；若於糖尿病腎硬化或嚴重硬化檢體中見到微弱瀰漫之 IgG 線狀著色，多為血漿蛋白非特異性滲漏吸附 (Pseudolinear pattern)，缺乏致病性抗體；Fibrillary GN 則為不規則之帶狀 (band-like) 螢光。
  • 主要是線條+線條旁邊有光暈
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• Granular(至少局部可看到一顆一顆) parietal deposition(Ig and complements)
  • Subendothelial
    • MPGN immunocomplex type, LN (典型表現為 IgG, IgA, IgM, C3, C1q 五種免疫反應物皆呈強陽性之 "full-house" 沉積〔Heptinstall's Pathology of the Kidney 8th ed 2023 Ch 14; Weening JJ et al. JASN 2004, PMID 14747370〕), cryoglobulin...
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  • Subepithelial
    • PSGN
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    • MGN(也有intramembranous deposits)
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  • Mesangial deposits
    • 可見於LN type II, MGN(?, 理論上應該沒有, 除非是一些secondary MGN), MCD(有一些non-specific deposits(所以intensity多不強); and its variants: IgM nephropathy, C1q nephropathy), mesangial GN with C3 deposits, resolving PSGN, IgA nephropathy or ......(參glomerulus(LM)的Mesangial cellular proliferation)
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  • Tubular/Interstitial deposits
    • 多是LN, or other autoimmunes
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• PSGN也是granular pattern depositions of IgG and C3, 不過有三種pattern(好像不重要, 無關預後)
  • Garland(花環) pattern(capillary wall)
    • 容易有nephrotic syndrome
    • Pericapillary loops:
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  • Starry sky pattern
    • Less severe
    • Capillary wall + mesangium
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  • Mesangial pattern
    • Resolving: LM此時多為isolated mesangial proliferation
    • mesangium
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