Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis
(2007) In Kidney International 71(7). p.664-672- Abstract
- Antibodies to double-stranded (dsDNA) are associated with systemic lupus erythematosus (SLE) and directly involved in human lupus nephritis. Information about their glomerular target antigens is inconsistent, and whether availability of target antigens, antibody specificity or avidity are nephritogenic parameters, is not determined. In this study, we analyzed renal tissue from anti-dsDNA antibody-positive lupus patients with nephritis by morphological and immunological assays, including immune electron microscopy (IEM) and colocalization IEM, an EM-based confocal microscopy assay. IEM demonstrated that antibody deposits were confined to electron dense structures (EDS) in glomerular membranes. These autoantibodies colocalized with... (More)
- Antibodies to double-stranded (dsDNA) are associated with systemic lupus erythematosus (SLE) and directly involved in human lupus nephritis. Information about their glomerular target antigens is inconsistent, and whether availability of target antigens, antibody specificity or avidity are nephritogenic parameters, is not determined. In this study, we analyzed renal tissue from anti-dsDNA antibody-positive lupus patients with nephritis by morphological and immunological assays, including immune electron microscopy (IEM) and colocalization IEM, an EM-based confocal microscopy assay. IEM demonstrated that antibody deposits were confined to electron dense structures (EDS) in glomerular membranes. These autoantibodies colocalized with nucleosome-binding anti-dsDNA/-histone/-transcription factor antibodies. To confirm the colocalization IEM-data, we developed a colocalization terminal deoxynucleotidyltransferase (TdT) biotin-dUTP nicked end-labeled (TUNEL) IEM assay where extracellular DNA was traced by TdT-mediated introduction of biotinylated nucleotides and autoantibodies by IEM. Results consistently demonstrated that DNA colocalized with autoantibodies in glomerular membrane-associated EDS. The colocalization IEM and colocalization TUNEL IEM assays thus demonstrate that intra-glomerular membrane-associated nucleosomes are targeted by anti-dsDNA autoantibodies in human lupus nephritis. The data provide a new approach to understand basic molecular and immunological processes accounting for antibody-mediated nephritis in human SLE. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/667456
- author
- Kalaaji, M. ; Fenton, K. A. ; Mortensen, E. S. ; Olsen, R. ; Sturfelt, Gunnar LU ; Alm, Per LU and Rekvig, O. P.
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- immunology and pathology, systemic lupus erythematosus, nephritis, immune complexes, glomerulus
- in
- Kidney International
- volume
- 71
- issue
- 7
- pages
- 664 - 672
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000245501900012
- scopus:33947660078
- ISSN
- 1523-1755
- DOI
- 10.1038/sj.ki.5002133
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Department of Rheumatology (013036000)
- id
- e21e3365-4746-4f45-a0d3-6cd5a83a9fad (old id 667456)
- date added to LUP
- 2016-04-01 15:26:57
- date last changed
- 2022-02-12 08:00:24
@article{e21e3365-4746-4f45-a0d3-6cd5a83a9fad,
abstract = {{Antibodies to double-stranded (dsDNA) are associated with systemic lupus erythematosus (SLE) and directly involved in human lupus nephritis. Information about their glomerular target antigens is inconsistent, and whether availability of target antigens, antibody specificity or avidity are nephritogenic parameters, is not determined. In this study, we analyzed renal tissue from anti-dsDNA antibody-positive lupus patients with nephritis by morphological and immunological assays, including immune electron microscopy (IEM) and colocalization IEM, an EM-based confocal microscopy assay. IEM demonstrated that antibody deposits were confined to electron dense structures (EDS) in glomerular membranes. These autoantibodies colocalized with nucleosome-binding anti-dsDNA/-histone/-transcription factor antibodies. To confirm the colocalization IEM-data, we developed a colocalization terminal deoxynucleotidyltransferase (TdT) biotin-dUTP nicked end-labeled (TUNEL) IEM assay where extracellular DNA was traced by TdT-mediated introduction of biotinylated nucleotides and autoantibodies by IEM. Results consistently demonstrated that DNA colocalized with autoantibodies in glomerular membrane-associated EDS. The colocalization IEM and colocalization TUNEL IEM assays thus demonstrate that intra-glomerular membrane-associated nucleosomes are targeted by anti-dsDNA autoantibodies in human lupus nephritis. The data provide a new approach to understand basic molecular and immunological processes accounting for antibody-mediated nephritis in human SLE.}},
author = {{Kalaaji, M. and Fenton, K. A. and Mortensen, E. S. and Olsen, R. and Sturfelt, Gunnar and Alm, Per and Rekvig, O. P.}},
issn = {{1523-1755}},
keywords = {{immunology and pathology; systemic lupus erythematosus; nephritis; immune complexes; glomerulus}},
language = {{eng}},
number = {{7}},
pages = {{664--672}},
publisher = {{Nature Publishing Group}},
series = {{Kidney International}},
title = {{Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis}},
url = {{http://dx.doi.org/10.1038/sj.ki.5002133}},
doi = {{10.1038/sj.ki.5002133}},
volume = {{71}},
year = {{2007}},
}