PATHOPHYSIOLOGY of the RENAL BIOPSY www.jasn.org Immune Complex Tubulointerstitial Nephritis Due to Autoantibodies to the Proximal Tubule Brush Border

Immune complex tubulointerstitial nephritis due to antibodies to brush border antigens of the proximal tubule has been demonstrated experimentally and rarely in humans. Our patient developed ESRD and early recurrence after transplantation. IgG and C3 deposits were conspicuous in the tubular basement membrane of proximal tubules, corresponding to deposits observed by electron microscopy. Rare subepithelial deposits were found in the glomeruli. The patient had no evidence of SLE and had normal complement levels. Serum samples from the patient reacted with the brush border of normal human kidney, in contrast with the negative results with 20 control serum samples. Preliminary characterization of the brush border target antigen excluded megalin, CD10, and maltase. We postulate that antibodies to brush border antigens cause direct epithelial injury, accumulate in the tubular basement membrane, and elicit an interstitial inflammatory response. J Am Soc Nephrol 27: ccc–ccc, 2015. doi: 10.1681/ASN.2015030334