Considered a pattern of immune mediated injury rather than a specific disease
MPGN is classified into groups
Type-I – characterised by deposition of immune complexes containing Ig G and complement
Type –II (Dense deposit disease)-In this activation of complement is an important factor.This belongs the group of disorders called C3 glomerulopathies
Pathogenesis
Pathogenesis – Type I MPGN
Immune complex of IgG and complement gets deposited in the glomeruli and there is activation of both classical and alternate pathways of complement activation
Antigens involved are unknown but believed to be proteins derived from infectious agents such as hepatitis C and B viruses which behave either as planted antigen often first binding to or being trapped with in glomerular structures or are contained in performed immune complexes deposited from the circulation.
Pathogenesis – Type II MPGN
In this there is activation of alternate complement pathway
C3 is converted to C3bBb by bacterial polysacharides, endotoxins and IgA aggregates in the presence of factors B, D and magnesium
C3bBb also called C3 convertase whose degradation is prevented by circulating autoantibody, C3 nephritic fator (C3NeF) thus causing activation of the alternative pathway
There is continuous degradation of C3 to C3b by C3 convertase producing hypocomplementemia
However how C3NeF is related to the nature of glomerular injury and dense deposits is still unknown
Morphology
Glomeruli are large and hypercellular
Hypercellularity is produced both by proliferation of both cells in mesangium and so called endothelial proliferation involving capillary endothelium and infiltrating leukocytes.
Glomeruli have an “lobular“ appearance due to the proliferative mesangial cells and increased mesangial matrix.
GBM is thickened and often shows a “double contour” or “form track” appearance especially evident in silver or PAS stains .This is caused by “duplication” of the basement membrane (also referred to as splitting) usually as a result of BM synthesis in response to subendothelial deposits of immune complexes.
Type I MPGN:
Electron microscopy: Characterised by the presence of discrete subendothelial electron dense deposits
Mesangial and occasional subepithelial deposits may also be present
Immunoflouresence shows IgG, IgM and C3 deposited in a glanular pattern and every complement components (C1Q and C4) are often also present indicating are immune complexes pathogenesis
Type II MPGN
Is characterised by deposition of dark, ribbon like electron dense material in the central layer of (Lamina Densa) of glomerular basement membrane
Immunofluorescence – C3 deposition on both sides of the basement membrane in irregular granular or linear pattern
C3 can also be identified in mesangium in the ring shaped aggregates
Clinical features:
Most patients with primary MPGN present as in adolescence or as young adults with nephrotic syndrome and a nephritic component manifested by hematuria
Disease may undergo remission or may follow slowly progressive but unremitting course
50% develop Chronic renal failure within 10 years
Reference
Vinay kumar, Abul K.Abbas, Nelson Fausto, Jon C. Aster. Robbins and Cotran Pathologic basis of disease. 8th edition.
Harsh mohan. Text book of Pathology.8th edition.2019
A.K.Mandal, Dr. Sharmana Choudhary. Textbook of Pathology for MBBS. Vol II. Second edition 2017.
