40 y/o with PMH significant for hep C -untreated and recent history of sore throat presents with photosensitivity rash and generalized weakness. Evaluation shows AKI, anemia, hypercalcemia and SPEP with M spike.UA shows dysmorphic RBC. Serologies are pending !
What could be the etiology of the suspected GN !
a) Hep C related MPGN
b) Post streptococcal GN
c) Lupus nephritis
d) proliferative GN related to Monoclonal gammapathy
e) Cryoglobulinemic GN related to HepC, Lupus or Monoclonal gammapathy.
This imaginary case brings to focus the diagnosis of GN based on immune deposit.
Of course, the clinical presentation and serologies will indicate the possible diagnosis in real clinical situation! The case presented above and the following explanation is purely for understanding the immune deposits based classification of GN (Which is very useful in teasing out the etiology of GN)
1) Light microscopy in all possible diagnosis may show proliferative GN
2) Immunofluorescence may show
a) Immune complex mediated disease process( by which I mean immunoglobulin deposition +/_ c3 deposition
If IgA dominant ———–> IgA nephropathy or IgA dominant post infectious GN( Staph super antigen and such)
If IgG dominant and monoclonal (Either kappa or lambda and not both)——-> Monoclonal gammapathy associated proliferative GN
If IgG dominant and polyclonal (both kappa and lambda)——–> Post infectious GN
If IgM dominant and polyclonal ——————————> Chronic infection such as hepatitis and autoimmune disease
If IgA, IgG, IgM (all Ig classes, C3 and C4- full house or partly full house in appropriate clinical setting)——-> Lupus nephritis and other auto immune diseases
b) No or negligible immune deposit ; pauci-immune GN ——————> ANCA + or ANCA – vasculitis
c) Complement mediated (by which I mean trace or minimal Ig deposit)
C3 dominant with minimal immunoglobulin of any subtype C3 GN or DDD
This understanding of immunofluorescence finding coupled with location of immune deposit in EM and complement levels will aid the diagnosis
C3 low and C4 normal—-> post infectious GN or shunt nephritis( typically staph epidermidis in patients with chronic shunt)
C4 low and C3 normal or low normal —-> Cryoglobulinemic GN from any cause(Polyclonal gammapathy, Hep C or auto immune)
Both C3 and C4 low —-> lupus nephritis
Normal complements—> ANCA + or ANCA – pauci-immune vasculitis, Good pasture disease(anti-GBM mediated), IgA nephritis or Infective endocarditis related GN which most commonly presents as pauci-immune GN.
Positive cryoglobulin in blood may or may not be pathogenic unless demonstrated as deposits in glomerular capillary loop!
Hope this helps in understanding the immune deposits in GN and its role in identifying the etiology of proliferative GN in a complex case as the one mentioned above.