Friday, February 17, 2017

Topic Discussion: Linear staining on IF and the differential diagnosis


Linear Staining in IF on renal pathology differential diagnosis



Image result for linear staining IF




Classically the linear staining in taught in medical schools to be associated with anti GBM disease.

On a recent discussion on ASN-Communities on this topic by many glomerular experts led to generating a differential on other causes of IF linear staining when anti GBM serologies are negative.

Dr. Richard Glassock summarized the other causes on the forum as listed below with a few references:

1)    Atypical anti-GBM disease- This entity recently described by Nasr et al in 2016 is a more indolent form of Anti GBM disease where there are no serological markers for anti GBM and there is linear staining. It’s a slower disease and better renal outcomes compared to classic GBM disease. The light microscopy is variable from MPGN, TMA, to endocapillary proliferation and distinct lack of crescents. Some cases had deposits and some didn’t. 50% of these cases have a monoclonal disorder
2) Fibrillary GN with "pseudo-linear" IgG deposits, often secondary to autoimmunity, infection or cancer
3) IgG4 Anti-GBM disease- most assays do not detect IgG4 anti-GBM antibody 
5) Monoclonal IgG or IgA kappa directed to COLIValpha1/2 chains 
6) Wrong substrate, poor sensitivity, prozone phenomenon  in IF assays
7) "Immune sink" where all circulating antibody is bound to GBM sites in vivo-serial testing will often resolve this
8) Spontaneous decay of circulating antibody levels with persistence of tissue deposited antibody 
9) Diabetic Nephropathy: a physico-chemical alteration of GBM or IgG causing non-specific deposition of IgG (and albumin)


Other references



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