Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis

M. Kalaaji, K. A. Fenton, E. S. Mortensen, R. Olsen, Gunnar Sturfelt, Per Alm, O. P. Rekvig

Research output: Contribution to journalArticlepeer-review

140 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)664-672
JournalKidney International
Volume71
Issue number7
DOIs
Publication statusPublished - 2007

Bibliographical note

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)

Subject classification (UKÄ)

  • Urology and Nephrology

Keywords

  • immunology and pathology
  • systemic lupus erythematosus
  • nephritis
  • immune complexes
  • glomerulus

Fingerprint

Dive into the research topics of 'Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis'. Together they form a unique fingerprint.

Cite this