Anti-LRP2 Nephropathy With Abundant IgG4-Positive Plasma Cells

A Case Report

Kumar P. Dinesh, Dean Raniele, Kendall Michels, Rupali S. Avasare, Christopher P. Larsen, Robert Kayton, Mazdak Khalighi, Nicole Andeen

Research output: Contribution to journalArticle

Abstract

In older adults, the most common kidney biopsy diagnoses include pauci-immune crescentic glomerulonephritis, membranous nephropathy, and focal segmental glomerulosclerosis. Recently, investigators described a small series of older patients (aged 66-80 years) with acute kidney injury and a kidney biopsy demonstrating tubular basement membrane (TBM) immune deposits of polytypic immunoglobulin G (IgG) and C3, acute tubular injury, and tubulointerstitial inflammation. They identified a circulating antibody against kidney tubular low-density lipoprotein (LDL) receptor-related protein 2 (LRP2; also known as megalin) in patients’ sera and colocalization of LRP2 with IgG in TBM deposits. We present a rare case of anti-LRP2 nephropathy/anti–brush border antibody disease and describe the novel feature of abundant IgG4-positive interstitial plasma cells. Along with the combination of TBM deposits, tubulointerstitial nephritis (TIN), and segmental glomerular subepithelial immune deposits seen in both entities, this newly described feature adds to the morphologic overlap with IgG4-related TIN. Identification of large TBM deposits using light microscopy and IgG staining of apical aspects of proximal tubules using immunofluorescence microscopy can point to the correct diagnosis of anti-LRP2 nephropathy and prompt confirmatory studies. Particularly in older patients with immune complex–mediated TIN who lack clinical, laboratory, radiographic, and/or characteristic histologic features of IgG4-TIN or other autoimmune, infectious, or drug-related injury, a diagnosis of anti-LRP2 nephropathy should be considered.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StatePublished - Jan 1 2019

Fingerprint

Plasma Cells
Interstitial Nephritis
Immunoglobulin G
Basement Membrane
Low Density Lipoprotein Receptor-Related Protein-2
Kidney
Border Disease
Biopsy
Focal Segmental Glomerulosclerosis
Membranous Glomerulonephritis
Antibodies
Wounds and Injuries
Glomerulonephritis
Fluorescence Microscopy
Acute Kidney Injury
Microscopy
Research Personnel
Staining and Labeling
Inflammation
Light

Keywords

  • anti-brush border antibody (ABBA)
  • anti-LRP2 nephropathy
  • case report
  • diagnostic error
  • IgG4
  • immune deposits
  • interstitial plasma cells
  • kidney biopsy
  • LDL receptor-related protein 2 (LRP2)
  • megalin
  • megalin

ASJC Scopus subject areas

  • Nephrology

Cite this

Anti-LRP2 Nephropathy With Abundant IgG4-Positive Plasma Cells : A Case Report. / Dinesh, Kumar P.; Raniele, Dean; Michels, Kendall; Avasare, Rupali S.; Larsen, Christopher P.; Kayton, Robert; Khalighi, Mazdak; Andeen, Nicole.

In: American Journal of Kidney Diseases, 01.01.2019.

Research output: Contribution to journalArticle

Dinesh, Kumar P. ; Raniele, Dean ; Michels, Kendall ; Avasare, Rupali S. ; Larsen, Christopher P. ; Kayton, Robert ; Khalighi, Mazdak ; Andeen, Nicole. / Anti-LRP2 Nephropathy With Abundant IgG4-Positive Plasma Cells : A Case Report. In: American Journal of Kidney Diseases. 2019.
@article{72927b5db0d643c381690dceece646a8,
title = "Anti-LRP2 Nephropathy With Abundant IgG4-Positive Plasma Cells: A Case Report",
abstract = "In older adults, the most common kidney biopsy diagnoses include pauci-immune crescentic glomerulonephritis, membranous nephropathy, and focal segmental glomerulosclerosis. Recently, investigators described a small series of older patients (aged 66-80 years) with acute kidney injury and a kidney biopsy demonstrating tubular basement membrane (TBM) immune deposits of polytypic immunoglobulin G (IgG) and C3, acute tubular injury, and tubulointerstitial inflammation. They identified a circulating antibody against kidney tubular low-density lipoprotein (LDL) receptor-related protein 2 (LRP2; also known as megalin) in patients’ sera and colocalization of LRP2 with IgG in TBM deposits. We present a rare case of anti-LRP2 nephropathy/anti–brush border antibody disease and describe the novel feature of abundant IgG4-positive interstitial plasma cells. Along with the combination of TBM deposits, tubulointerstitial nephritis (TIN), and segmental glomerular subepithelial immune deposits seen in both entities, this newly described feature adds to the morphologic overlap with IgG4-related TIN. Identification of large TBM deposits using light microscopy and IgG staining of apical aspects of proximal tubules using immunofluorescence microscopy can point to the correct diagnosis of anti-LRP2 nephropathy and prompt confirmatory studies. Particularly in older patients with immune complex–mediated TIN who lack clinical, laboratory, radiographic, and/or characteristic histologic features of IgG4-TIN or other autoimmune, infectious, or drug-related injury, a diagnosis of anti-LRP2 nephropathy should be considered.",
keywords = "anti-brush border antibody (ABBA), anti-LRP2 nephropathy, case report, diagnostic error, IgG4, immune deposits, interstitial plasma cells, kidney biopsy, LDL receptor-related protein 2 (LRP2), megalin, megalin",
author = "Dinesh, {Kumar P.} and Dean Raniele and Kendall Michels and Avasare, {Rupali S.} and Larsen, {Christopher P.} and Robert Kayton and Mazdak Khalighi and Nicole Andeen",
year = "2019",
month = "1",
day = "1",
doi = "10.1053/j.ajkd.2018.12.039",
language = "English (US)",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Anti-LRP2 Nephropathy With Abundant IgG4-Positive Plasma Cells

T2 - A Case Report

AU - Dinesh, Kumar P.

AU - Raniele, Dean

AU - Michels, Kendall

AU - Avasare, Rupali S.

AU - Larsen, Christopher P.

AU - Kayton, Robert

AU - Khalighi, Mazdak

AU - Andeen, Nicole

PY - 2019/1/1

Y1 - 2019/1/1

N2 - In older adults, the most common kidney biopsy diagnoses include pauci-immune crescentic glomerulonephritis, membranous nephropathy, and focal segmental glomerulosclerosis. Recently, investigators described a small series of older patients (aged 66-80 years) with acute kidney injury and a kidney biopsy demonstrating tubular basement membrane (TBM) immune deposits of polytypic immunoglobulin G (IgG) and C3, acute tubular injury, and tubulointerstitial inflammation. They identified a circulating antibody against kidney tubular low-density lipoprotein (LDL) receptor-related protein 2 (LRP2; also known as megalin) in patients’ sera and colocalization of LRP2 with IgG in TBM deposits. We present a rare case of anti-LRP2 nephropathy/anti–brush border antibody disease and describe the novel feature of abundant IgG4-positive interstitial plasma cells. Along with the combination of TBM deposits, tubulointerstitial nephritis (TIN), and segmental glomerular subepithelial immune deposits seen in both entities, this newly described feature adds to the morphologic overlap with IgG4-related TIN. Identification of large TBM deposits using light microscopy and IgG staining of apical aspects of proximal tubules using immunofluorescence microscopy can point to the correct diagnosis of anti-LRP2 nephropathy and prompt confirmatory studies. Particularly in older patients with immune complex–mediated TIN who lack clinical, laboratory, radiographic, and/or characteristic histologic features of IgG4-TIN or other autoimmune, infectious, or drug-related injury, a diagnosis of anti-LRP2 nephropathy should be considered.

AB - In older adults, the most common kidney biopsy diagnoses include pauci-immune crescentic glomerulonephritis, membranous nephropathy, and focal segmental glomerulosclerosis. Recently, investigators described a small series of older patients (aged 66-80 years) with acute kidney injury and a kidney biopsy demonstrating tubular basement membrane (TBM) immune deposits of polytypic immunoglobulin G (IgG) and C3, acute tubular injury, and tubulointerstitial inflammation. They identified a circulating antibody against kidney tubular low-density lipoprotein (LDL) receptor-related protein 2 (LRP2; also known as megalin) in patients’ sera and colocalization of LRP2 with IgG in TBM deposits. We present a rare case of anti-LRP2 nephropathy/anti–brush border antibody disease and describe the novel feature of abundant IgG4-positive interstitial plasma cells. Along with the combination of TBM deposits, tubulointerstitial nephritis (TIN), and segmental glomerular subepithelial immune deposits seen in both entities, this newly described feature adds to the morphologic overlap with IgG4-related TIN. Identification of large TBM deposits using light microscopy and IgG staining of apical aspects of proximal tubules using immunofluorescence microscopy can point to the correct diagnosis of anti-LRP2 nephropathy and prompt confirmatory studies. Particularly in older patients with immune complex–mediated TIN who lack clinical, laboratory, radiographic, and/or characteristic histologic features of IgG4-TIN or other autoimmune, infectious, or drug-related injury, a diagnosis of anti-LRP2 nephropathy should be considered.

KW - anti-brush border antibody (ABBA)

KW - anti-LRP2 nephropathy

KW - case report

KW - diagnostic error

KW - IgG4

KW - immune deposits

KW - interstitial plasma cells

KW - kidney biopsy

KW - LDL receptor-related protein 2 (LRP2)

KW - megalin

KW - megalin

UR - http://www.scopus.com/inward/record.url?scp=85062712611&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062712611&partnerID=8YFLogxK

U2 - 10.1053/j.ajkd.2018.12.039

DO - 10.1053/j.ajkd.2018.12.039

M3 - Article

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

ER -