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LDL Receptor-Related Protein 2 (Megalin) as a Target Antigen in Human Kidney Anti-Brush Border Antibody Disease
- Source :
- Journal of the American Society of Nephrology. 29:644-653
- Publication Year :
- 2017
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2017.
-
Abstract
- Primary renal tubulointerstitial disease resulting from proximal tubule antigen-specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who 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. All but one of the patients also had segmental glomerular deposits on renal biopsy specimen. Patients with ABBA disease were elderly and presented with AKI and subnephrotic proteinuria. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that we identified as LDL receptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry. Immunostaining revealed that LRP2 specifically colocalized with IgG in the tubular immune deposits on the ABBA biopsy specimen but not the control specimen analyzed. Finally, ABBA serum samples but not control samples showed reactivity against recombinantly expressed N-terminal LRP2 fragments on Western blots and immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This case series details the clinicopathologic findings of patients with ABBA disease and shows that the antigenic target of these autoantibodies is LRP2. Future studies are needed to determine the disease prevalence, stimulus for ABBA, and optimal treatment.
- Subjects :
- Male
0301 basic medicine
Pathology
medicine.medical_specialty
030232 urology & nephrology
Immune complex formation
Basement Membrane
Kidney Tubules, Proximal
03 medical and health sciences
0302 clinical medicine
Membranous nephropathy
medicine
Humans
Aged
Autoantibodies
Aged, 80 and over
Kidney
Microvilli
biology
medicine.diagnostic_test
business.industry
General Medicine
Acute Kidney Injury
medicine.disease
LRP2
Low Density Lipoprotein Receptor-Related Protein-2
030104 developmental biology
medicine.anatomical_structure
Nephrology
Immunoglobulin G
biology.protein
Nephritis, Interstitial
Female
Renal biopsy
Antibody
business
Tubulointerstitial Disease
Kidney disease
Subjects
Details
- ISSN :
- 15333450 and 10466673
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Journal of the American Society of Nephrology
- Accession number :
- edsair.doi.dedup.....ffda96aba6de6f50925916f619f9f643