Clinicopathologic Features of Antibrush Border Antibody Disease

Abstract

Introduction: Antibrush border antibody disease (ABBA) is an autoimmune tubulointerstitial kidney disease that primarily affects older individuals and results in progressive kidney failure. It is rare with only 20 reported cases. Here, we describe a case series to further define the clinicopathologic spectrum and natural history, and to inform management.

Methods: We identified 67 patients with ABBA who underwent kidney biopsy, including 65 native and 2 transplants. Demographics, clinical findings, and laboratory data were obtained. Histopathologic data included light microscopy, immunofluorescence, electron microscopy and immunostaining for LRP2, CUBN, and AMN. Follow-up data, including treatment(s), laboratory values, and outcomes, were available from 51 patients.

Results: Patients with ABBA were predominantly male with a median age of 72 years. Median serum creatinine was 2.7 mg/dl, proteinuria was 2.8 g/day, and hematuria was present in two-thirds of the patients. Tubular injury with LRP2-positive tubular basement membrane (TBM) deposits were seen in 94.2% of patients. Thirty-eight patients (56.7%) had a second kidney disease, commonly glomerular diseases with high-grade proteinuria. These diseases included podocytopathies, membranous nephropathy (MN), IgA nephropathy, diabetic glomerulopathy, lupus nephritis (LN), crescentic glomerulonephritis (GN), tubulointerstitial nephritis, and involvement by lymphoma. The majority of patients were treated with immunosuppression. Of those patients with follow-up, 29.4% achieved remission, 70.6% had no response, and 52.8% required dialysis or were deceased. Untreated patients were at the highest risk.

Conclusion: ABBA is a rare autoimmune kidney disease that often occurs with other kidney diseases. Although the overall prognosis of ABBA is poor, there is potential benefit from immunosuppression.

Keywords: ABBA; AMN; CUBN; LRP2; antibrush border antibody disease; kidney biopsy.

Graphical abstract

Figure 1

Microscopic features of typical ABBA. (a) Acute tubular injury with epithelial simplification, tubular dilatation, and interstitial edema (hematoxylin and eosin stain, original magnification 400x, scale bar = 20 μm). (b) Acute on chronic tubular injury with increased spacing between injured tubules due to interstitial fibrosis (Masson-Trichrome-stain, original magnification 100x, scale bar = 100 μm). (c) Unremarkable glomerulus (Periodic acid-Schiff reaction, original magnification 400x, scale bar = 20 μm). (d) Focal segmental vacuoles along the glomerular capillary loops consistent with intramembranous immune deposits (arrows, Jones methenamine Silver stain, original magnification 600x, scale bar = 20 μm). (e) Electron photomicrograph showing subepithelial and intramembranous electron-dense immune-type deposits with podocyte foot process effacement (unstained section original magnification 12000x, scale bar = 5 μm). (f) Electron photomicrograph displaying large TBM deposits (unstained section original magnification 12000x).

Figure 2

Classic immunofluorescence features of ABBA. (a) IgG staining along TBMs and proximal tubular brush borders (fluorescein-conjugated anti-human IgG, original magnification 200x, scale bar = 50 μm). (b) IgG staining highlighting proximal tubular brush border and tubular epithelial cell cytoplasm (fluorescein-conjugated anti-human IgG, original magnification 400x, scale bar = 20 μm). (c) Granular IgG staining along TBMs and Bowman's capsule of a glomerulus (fluorescein-conjugated anti-human IgG, original magnification 200x, scale bar = 50 μm. (d) Segmental IgG staining along glomerular capillary loops and Bowman's capsule (fluorescein-conjugated anti-human IgG, original magnification 400x, scale bar = 20 μm). (e) LRP2 staining highlighting TBM deposits in addition to proximal tubular brush border staining (paraffin immunofluorescence staining for LRP2, original magnification 600x, scale bar = 20 μm). (f) Indirect immunofluorescence of ABBA sera demonstrates seroreactivity against the proximal tubular brush borders of normal human kidney (fluorescence conjugated anti-human IgG, original magnification 200x, scale bar = 50 μm).

Figure 3

IgG subclass staining in selected cases of ABBA. (a) IgG4 dominant staining along proximal tubular brush borders (fluorescein-conjugated anti-human IgG1/2/3/4 subclass antibodies, original magnification 400x, scale bar = 20 μm). (b) IgG1 and IgG4 co-dominant staining along proximal tubular brush borders (fluorescein-conjugated anti-human IgG1/2/3/4 subclass antibodies, original magnification 400x, scale bar = 20 μm).

Figure 4

Histopathologic spectrum of tubulointerstitial findings in ABBA. (a) Mild acute tubular injury, characterized by apical cytoplasmic blebbing and attenuation of brush borders of the proximal tubules (PAS stain, original magnification 200x, scale bar = 50 μm). (b) Acute on chronic tubular injury with interstitial fibrosis and edema separating tubular profiles, epithelial simplification, and dilation (hematoxylin and eosin stain, original magnification 200 x, scale bar = 50 μm). (c) Granulomatous interstitial nephritis, characterized by lymphocytic interstitial inflammation, epitheliod histiocytes, and a giant cell reaction (PAS stain, original magnification 400x, scale bar = 20 μm). (d) Dense monomorphic lymphoid infiltrate within interstitium (hematoxylin and eosin stain, original magnification 400x, scale bar = 20 μm). (e) CD3 immunohistochemistry of the case shown in (d) demonstrating CD3+ T cells make up the minority of the interstitial lymphoid infiltrate (CD3 immunoperoxidase staining, original magnification 40x, scale bar = 200 μm). (f) CD20 immunohistochemistry of the case shown in (d) and (e) showing a predominance of CD20+ B cells within the lymphoid infiltrate, consistent with involvement by a low-grade B cell lymphoma in a patient with known lymphoplasmacytic lymphoma (CD20 immunoperoxidase staining, original magnification 40x, scale bar = 200 μm). ABBA, antibrush border antibody disease; PAS, periodic acid-Schiff; TBM, tubular basement membrane.