Abstract: FR-PO090

Low-Density Lipoprotein Receptor-Related 2 (Megalin) as Target Antigen in Human Kidney Anti-Brush Border Antibody Disease

Session Information

  • AKI Clinical: Predictors
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Trivin-Avillach, Claire, Boston University Medical Center, Boston, Massachusetts, United States
  • Cossey, Nicholas, Arkana Laboratories, Little Rock, Arkansas, United States
  • Rosales, Ivy A., Massachusetts General Hospital , Boston, Massachusetts, United States
  • Wooldridge, Thomas D., Nephrology & Hypertension Associates, LTD, Tupelo, Mississippi, United States
  • Walker, Patrick D., Arkana Laboratories, Little Rock, Arkansas, United States
  • Colvin, Robert B., Massachusetts General Hospital , Boston, Massachusetts, United States
  • Klein, Jon B., University of Louisville Medicine, Louisville, Kentucky, United States
  • Salant, David J., Boston University Medical Center, Boston, Massachusetts, United States
  • Beck, Laurence H., Boston University Medical Center, Boston, Massachusetts, United States
  • Larsen, Christopher Patrick, Arkana Laboratories, Little Rock, Arkansas, United States
  • Coles, Paige A., Boston University Medical Center, Boston, Massachusetts, United States
  • Collins, A. Bernard, Massachusetts General Hospital , Boston, Massachusetts, United States
  • Merchant, Michael, University of Louisville Medicine, Louisville, Kentucky, United States
  • Ma, Hong, Boston University Medical Center, Boston, Massachusetts, United States
  • Wilkey, Daniel Wade, University of Louisville Medicine, Louisville, Kentucky, United States
  • Ambruzs, Josephine M., Arkana Laboratories, Little Rock, Arkansas, United States
  • Messias, Nidia Cordeiro, Nephrology Associates, PLC, Little Rock, Arkansas, United States
Background

Acute kidney injury (AKI) has a broad differential diagnosis. Autoimmune diseases against glomerular antigens are well recognized but tubular injury as a result of direct immunologic insult is not part of the routine evaluation. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney anti-brush border antibodies and renal failure (ABBA disease).

Methods

Ten cases of ABBA disease were identified that had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border. Immunoblotting of a protein extract from human tubular cells was performed with serum from cases and controls, and immunoprecipitation followed by mass spectrometry was used to identify the protein targeted by the anti-brush border antibodies. Cell expression of recombinant protein followed by immunoblotting and immunoprecipitation was used to confirm the identity of the antigen.

Results

Patients with ABBA disease were elderly (mean age 72.9 years), presented with acute kidney injury (median serum creatinine 4.0 mg/dl) and moderate proteinuria. The kidney biopsy showed acute tubular injury with apical cytoplasmic blebbing, loss of brush border, regenerative changes and granular IgG and C3 deposits along tubular basement membranes. All patient sera were reactive to the proximal tubular brush border on sections of normal human kidney. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that was identified as low-density lipoprotein receptor-related 2 (LRP2) by immunoprecipitation and mass spectrometry. Recombinant expression of an N-terminal recombinant fragment of LRP2 was used to confirm this finding by Western blot and immunoprecipitation. LRP2 specifically co-localized with IgG in the tubular immune deposits.

Conclusion

We present the first case series detailing the clinicopathologic findings of patients with ABBA disease and show that the antigenic target of these autoantibodies is LRP2.

Funding

  • NIDDK Support