Kidney nontumor
Tubulointerstitial diseases - Immunologic
Anti-brush border antibody disease/Anti-LRP2 nephropathy


Topic Completed: 9 September 2019

Revised: 9 September 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Anti-brush border antibody disease

Alexander J. Gallan, M.D.
Page views in 2019 to date: 49
Cite this page: Gallan A. Anti-brush border antibody disease/Anti-LRP2 nephropathy (pending). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneyantibrushLRP2.html. Accessed November 20th, 2019.
Definition / general
  • Immune complex tubulointerstitial nephritis
  • Caused by antibodies against LDL-Receptor Related Protein 2 (LRP2) / megalin, a component of the proximal tubular brush border
Essential features
  • Presence of serum anti-brush border antibodies targeting LRP2 (J Am Soc Nephrol 2018;29:644)
  • Acute tubular injury with loss of brush borders, thickened tubular basement inflammation with focal tubulitis
  • Diffuse granular IgG and C3 immune complex deposits along tubular basement membranes (J Am Soc Nephrol 2016;27:380)
  • Focal glomerular subepithelial immune complex deposition
  • Often progresses to end stage kidney disease
Terminology
  • Anti-brush border antibody (ABBA) disease
  • ABBA tubulointerstitial nephritis
  • Anti-LRP2 nephropathy (more specific name)
ICD coding
Epidemiology
Sites
  • Kidney, tubules and glomeruli
Pathophysiology
  • Not well established
  • Circulating antibodies to LRP2 (component of brush border) causes tubular injury and immune complex deposition in tubular basement membranes
  • Immune complexes composed of IgG and C3 (mostly IgG4 subtype)
  • Scattered glomerular subepithelial immune complexes also present
  • Can cause progressive interstitial fibrosis and tubular atrophy, culminating in end stage kidney disease
  • May recur after transplant (J Am Soc Nephrol 2016;27:380)
Etiology
  • Idiopathic; no established triggers or associations
Clinical features
  • Progressive renal insufficiency
Diagnosis
  • Presence of serum anti-brush border antibodies targeting LRP2
  • Acute tubular injury with loss of brush borders, thickened tubular basement membranes and interstitial inflammation with focal tubulitis
  • Diffuse granular IgG and C3 immune complex deposits along tubular basement membranes
Laboratory
  • Elevated serum creatinine, slowly progressive decrease in glomerular filtration rate
  • Bland urine sediment
Prognostic factors
  • Progressive interstitial fibrosis and tubular atrophy in advanced cases
Case reports
Treatment
  • Immunosuppression and plasma exchange have limited utility
  • May recur after transplant
Microscopic (histologic) description
  • Acute tubular injury with loss of brush borders, thickened tubular basement membranes and interstitial inflammation with focal tubulitis
  • Variable but often severe interstitial fibrosis and tubular atrophy
  • Presence of abundant IgG4+ plasma cells has been described (Am J Kidney Dis 2019 Mar 12 [Epub ahead of print])
Microscopic (histologic) images

Contributed by Alexander J. Gallan, M.D.
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Tubular injury

Immunofluorescence description
  • Diffuse granular IgG and C3 immune complex deposits along tubular basement membranes (mostly IgG4 subclass)
  • Scattered glomerular subepithelial immune complexes also present
  • Patient serum reacts with normal human brush border (anti-brush border antibodies) (J Am Soc Nephrol 2016;27:380)
  • LRP2 co-localizes with tubular basement membrane immune complex deposits (J Am Soc Nephrol 2018;29:644)
Immunofluorescence images

Contributed by Alexander J. Gallan, M.D.
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TBM deposits

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Segmental glomerular capillary wall deposits

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Anti-brush border antibodies

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TBM deposits

Positive stains
  • PAS highlights thickened glomerular basement membranes
Negative stains
  • IgG/IgG4 immunostains: no increased ratio of IgG4/IgG positive plasma cells (< 40%)
  • SV40: negative for polyomavirus infection
Electron microscopy description
  • Prominent electron dense deposits in the proximal tubular basement membranes
  • Scattered glomerular subepithelial electron dense deposits
Electron microscopy images

Contributed by Alexander J. Gallan, M.D.
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TBM deposits

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Segmental glomerular subepithelial deposits

Sample pathology report
  • Kidney; biopsy:
    • Anti-LRP2 nephropathy
    • Focal global glomerular sclerosis
    • Severe interstitial fibrosis and tubular atrophy
  • Microscopic description: 15 glomeruli, 5 globally sclerosed (33%). Remaining glomeruli appear essentially normal. Tubular basement membranes show extensive tubular injury with loss of brush borders, mild interstitial inflammation with tubulitis and thickening of the tubular basement membranes. There is severe interstitial fibrosis and tubular atrophy.
  • Immunofluorescence microscopy: Granular to confluent tubular basement membrane staining for IgG and C3. IgG subclass staining demonstrates predominant IgG4 staining. Segmental granular glomerular basement membrane staining for IgG and C3 is also present.
  • Electron microscopy: Extensive electron dense deposits in proximal tubular basement membranes. Scattered glomerular subepithelial deposits with glomerular basement membrane spikes and focal podocyte foot process effacement.
Differential diagnosis
  • Lupus nephritis
    • Clinical diagnosis of lupus and positive lupus serologies
    • Usually predominantly glomerular immune complex deposition +/- tubular basement membrane deposits
    • "Full houseā€ immunofluorescence (positive for IgG, IgA, IgM, C3, C1q, and kappa and lambda light chains)
  • IgG4-related tubulointerstitial nephritis
    • Usually multi-organ involvement
    • Storiform fibrosis with IgG4+ plasma cells
    • ABBA/LRP2 negative
  • Idiopathic hypocomplementemic tubulointerstitial nephritis
    • Low complement levels
  • Giant cell tubulitis with tubular basement membrane deposits
    • Associated with aprotinin, a drug used to reduce bleeding during cardiac and liver surgeries
    • Multinucleated giant cells cuffing tubular basement membranes
  • Polyomavirus nephropathy
    • Occasional tubular basement membrane immune complex deposits
    • Transplant patients
    • Viral cytopathic effects, positive for SV40 immunostain
Additional references
Board review question #1
    Which of the following findings is seen in anti-brush border antibody tubulointerstitial nephritis?

  1. Diffuse glomerular subepithelial immune complex deposition without tubular basement membrane deposits
  2. Granular tubular basement membrane immunofluorescence staining for IgG and C3 with sparse glomerular subepithelial immune complex deposition
  3. Linear glomerular basement membrane and tubular basement membrane immunofluorescence staining for IgG and kappa only, with powdery electron dense deposits by electron microscopy
  4. Proliferative glomerulonephritis with full house immunofluorescence staining in the glomeruli, tubular basement membranes and arterioles
Board review answer #1
B. Granular tubular basement membrane immunofluorescence staining for IgG and C3 with sparse glomerular subepithelial immune complex deposition

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Reference: Anti-brush border antibody disease/Anti-LRP2 nephropathy
Board review question #2

    Which of the following best describes the pathophysiology of anti-brush border antibody tubulointerstitial nephritis?

  1. Patients develop autoantibodies against components of the alternative pathway of complement
  2. Patients develop autoantibodies against LRP2 / megalin, a component of the proximal tubular brush border
  3. Patients develop autoantibodies against podocyte antigen PLA2-R
  4. Patients develop mutations in the gene encoding LRP2 / megalin, a component of the proximal tubular brush border
Board review answer #2
B. Patients develop autoantibodies against LRP2 / megalin, a component of the proximal tubular brush border

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Reference: Anti-brush border antibody disease/Anti-LRP2 nephropathy
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