Membranous glomerulonephritis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

Pathophysiology

Phospholipase A2 receptor

• The M-type PLA2R is the major antigen in human idiopathic MN. It is expressed in glomerular podocytes.
• There was no colocalization of PLA2R in secondary MN biopsies.
• PLA2R antigen detected within immune deposits by immunofluorescence of the biopsy specimen. [26]
• Detection of the immune complex specificity is 100 percent.

Thrombospondin type-1

• THSD7A has been found in patients with idiopathic MN who are negative for anti-PLA2R antibodies.

Neutral endopeptidase

• Anti-neutral endopeptidase antibodies caused MN in the neonates.
• It resolves months after birth.

• The T helper-2 predominates in MN and minimal change disease.

Microscopic Pathology

• Early biopsies may be normal
• Later: uniform diffuse capillary wall thickening without hypercellularity, without mesangial sclerosis and without inflammatory cells
• Proximal convoluted tubules contain hyaline droplets, reflecting protein reabsorption
• With progression, get membrane thickening, narrow capillary lumina, mesangial sclerosis and glomerulosclerosis

Immunofluorescence

• Granular diffuse peripheral deposits, usually IgG and C3, also C5b-C9 and occasionally IgM or IgA
• C4d immunostaining may be diagnostic (Histol Histopathol 2011;26:1391) 

Stages

• Stage I: LM - normal for slightly thickened BM, slight GMB vacuolization; IF - fine granular IgG, C3; EM - scattered small subepithelial electron dense deposits, no foot process effacement or spikes
• Stage II: LM - moderately thickened BM with spikes and vacuolization; IF - moderate sized, granular IgG, C3; EM - diffuse spikes due to subepithelial deposits, diffuse foot process effacement
• Stage III: LM - markedly thickened GBM, residual spikes and vacuoles, chain like appearance; IF - coarsely granular IgG, C3; EM - intramembranous deposits, spikes, neomembrane formation and diffuse foot process effacement
• Stage IV: LM - markedly thickened GBM, few spikes, vacuoles and glomerulosclerosis; IF - focal IgG, C3; EM - sclerotic GBM, few deposits and lacunae

References

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  Membranous Glomerulonephritis: Electron micrography. An excellent example to show thickened basement membrane and immune complexes.

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  Membranous Glomerulonephritis: Micro trichrome high mag excellent to show thickened capillary basement membranes

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  Membranous Glomerulonephritis: Micro PAS high mag excellent example of this lesion

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  Membranous Glomerulonephritis: Micro PAS med mag