Diagnose This! (February 3, 2020)

What is your diagnosis?    ​ ​   ​   ​ ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​ ​   ​ ​   ​ ​   ​ ​     ​

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The immunofluorescence image shows an anti-LRP2 stain showing positive staining of the proximal tubular brush border along with staining of proximal tubular basement membrane deposits consistent with a diagnosis of Anti-Brush Border Antibody Disease (ABBA), also known as anti-LRP2 nephropathy. Anti-brush border antibody disease occurs secondary to autoantibodies targeted at the LDL receptor-related protein 2, or Megalin, on the proximal tubule brush border. A few other diseases known to have associated tubular basement membrane deposits would include lupus nephritis and IgG4-related tubulointerstitial nephritis; however, you would not expect to see staining of the proximal tubular brush border as seen here. The predominant histologic feature of ABBA disease by light microscopy is variable degrees of acute tubular injury along with tubular basement membrane deposits and proximal tubular brush border staining by immunofluorescence with IgG +/- C3 leading the pathologist to order the LRP2 stain and clinch the diagnosis. Interestingly, cases of ABBA frequently show segmental IgG and C3 staining of glomerular capillary loops with associated subepithelial deposits by electron microscopy. Occasionally, granular staining of Bowman’s capsule by immunofluorescence can also be seen, the significance of which is currently unknown. Clinically, ABBA is a rare disease seen more commonly in older males that leads to slowly progressive renal failure. Of note, this disease has also been shown to recur in the transplant setting.

Reference: Larsen CP, Trivin-Avillach C, Coles P, et al. LDL receptor-related protein 2 (Megalin) as a target antigen in human kidney anti-brush border antibody disease. J Am Soc Nephrol 2017; 29.