Impairment of genomic DNA binding to a putative dysfunctional receptor on erythrocytes independent of complement and antibodies in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is characterized by a variety of autoantibodies and other immune abnormalities indicative of an immunological hyperactivity. Antibodies against native DNA, however, are a disease-specific marker and play a major role in the pathogenesis of systemic or organ-specific disease manifestations. Nevertheless, the mechanisms causing the appearance of autoantibodies and immune complexes in SLE are not yet understood. Here, we report that chromosomal DNA and other forms of nucleic acids are usually cleared from circulation by binding to a yet unidentified receptor-like protein on the surface membrane of erythrocytes, independently from complement or antibodies. The binding kinetics of DNA and other nucleic acids to erythrocytes are significantly altered in SLE patients, showing an overall reduced binding capability and presaturated binding kinetics. Significant amounts of chromosomal DNA can be isolated from erythrocytes of SLE patients but not from normal controls. Electron microscopy shows electron-dense particles on the surface of SLE erythrocytes (approximate size 20-40 nm). Comparative genomic hybridization reveals that the nucleic acid isolated from erythrocytes of SLE patients is of genomic and random origin, leading to an accumulation of "free" nucleic acids in the periphery, which eventually induces a B-cell immune response.
Huss
R
R
Institute of Pathology, University of Munich, Germany. Ralf.Huss@lrz.uni-muenchen.de
Haas
C
C
Herrmann
M
M
Kalden
J R
JR
Löhrs
U
U
D000906:Antibodies / Q000502:physiology*; D003165:Complement System Proteins / Q000502:physiology*; D004247:DNA / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008854:Microscopy, Electron; D011956:Receptors, Cell Surface / Q000378:metabolism*
D000906:Antibodies; D011956:Receptors, Cell Surface; D003165:Complement System Proteins; D004247:DNA