Aarhus University Seal

Characterization of DNA-protein complexes by nanoparticle tracking analysis and their association with systemic lupus erythematosus

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Nanotechnology enables investigations of single biomacromolecules, but technical challenges have limited the application in liquid biopsies, for example, blood plasma. Nonetheless, tools to characterize single molecular species in such samples represent a significant unmet need with the increasing appreciation of the physiological importance of protein structural changes at nanometer scale. Mannose-binding lectin (MBL) is an oligomeric plasma protein and part of the innate immune system through its ability to activate complement. MBL also serves a role as a scavenger for cellular debris, especially DNA. This may link functions of MBL with several inflammatory diseases in which cell-free DNA now appears to play a role, but mechanistic insight has been lacking. By making nanoparticle tracking analysis possible in human plasma, we now show that superoligomeric structures of MBL form nanoparticles with DNA. These oligomers correlate with disease activity in systemic lupus erythematosus patients. With the direct quantification of the hydrodynamic radius, calculations following the principles of Taylor dispersion in the blood stream connect the size of these complexes to endothelial inflammation, which is among the most important morbidities in lupus. Mechanistic insight from an animal model of lupus supported that DNA-stabilized superoligomers stimulate the formation of germinal center B cells and drive loss of immunological tolerance. The formation involves an inverse relationship between the concentration of MBL superoligomers and antibodies to double-stranded DNA. Our approach implicates the structure of DNA-protein nanoparticulates in the pathobiology of autoimmune diseases.

Original languageEnglish
Article numbere2106647118
JournalProceedings of the National Academy of Sciences
Number of pages10
Publication statusPublished - Jul 2021

    Research areas

  • Nanotechnology | autoimmunity | mannan-binding lectin | systemic lupus erythematosus, COMPLEMENT, ACTIVATION, SERINE PROTEASES, RECOGNITION, DISPERSION, POLYVALENT BINDING, mannan-binding lectin&nbsp, MANNAN-BINDING LECTIN, systemic lupus erythematosus, nanotechnology&nbsp, autoimmunity&nbsp, NANOSCIENCE, LIGAND, COLLECTINS

See relations at Aarhus University Citationformats

ID: 220299327