A classification has introduced C3 glomerulopathy (C3 glomerulopathy consensus report) that
should be used to designate a disease process due to abnormal control of complement
activation, deposition, or degradation and characterized by predominant glomerular C3
fragment deposits with EM dense deposits. Also, the consensus suggested that the term
glomerulonephritis with dominant C3 should be used in practice as a morphological term for
those cases with dominant C3 (C3c satining) which is defined as C3 intensity ≥ 2 orders of
magnitude more than any other immune reactant on a scale of 0 to 3.
C3 glomerulonephritis with 3 dominant C3 deposits include C3 glomerulopathy, post-infectious
glomerulonephritis (PIGN) and others such as para-protein associated glomerulonephritis.
In C3 glomerulopathy; the alternative pathway plays a major role in pathogenesis of this
group of diseases. It occurs because of dysregulation of alternative complement pathway.
Dysregulation can be due to mutations of complement proteins or to autoantibodies that
promote complement activation.
Classical/lectin complement pathway has shown potential in evaluation of C3 glomerulopathy.
It's suggested that presence of glomerular C4d which is a product of early classical/lectin
pathway, should not exclude a C3 glomerulopathy.
Another disease group with prominent C3 deposits is postinfectious glomerulonephritis (PIGN)
and although PIGN has traditionally been thought of as a disease triggered by glomerular
immune complex deposition but C3 deposition in absence of immune complex deposits can be seen
in patients with PIGN but with the emergence of C3 glomerulonephritis (C3GN), the distinction
is difficult as the clinical and pathological presentation may be similar. However, their
treatment and clinical course vary significantly.
In addition there is overlap between PIGN and C3 glomerulopathy as they may both show
prominent sub-epithelial humps on electron microscopy. This overlap means that it may be very
difficult to decide on morphology alone whether a biopsy is a typical PIGN that will resolve,
or whether it represents a C3 glomerulopathy due to an underlying complement abnormality that
will lead to persistent glomerulonephritis.