Endogenous circulating DNA in systemic lupus erythematosus. Occurrence as multimeric complexes bound to histone.

Abstract

Little is known about endogenous systemic lupus erythematosus (SLE) plasma DNA even though it is the presumed precursor of DNA-containing immune complexes, thought to play a central role in lupus glomerulonephritis. DNA purified from SLE plasma formed discrete bands, corresponding to sizes of about 150-200, 400, 600, and 800 bp, closely resembling the characteristic 200 bp "ladder" found with oligonucleosomal (ON) DNA. By radiolabeling DNA while in whole plasma, the very small amounts present could be further characterized. All of 24 such specimens formed two or more discrete bands on 6% PAGE. Detergent treatment of plasma resulted in a DNA migration pattern similar to that of purified DNA, suggesting disruption of DNA-protein complexes. DNA purified from authentic ON and detergent-treated ON behaved similarly. A significant portion of DNA, labeled in SLE plasma could be specifically immunoprecipitated with monoclonal antihistone antibody as was the case with ON. These immunoprecipitates, when redissolved, exhibited the expected size distribution upon PAGE. It is concluded that DNA in SLE plasma occurs as a series of multimeric complexes, at least a portion of which is noncovalently bound to histone. These results are consistent with an ON-like structure for SLE plasma DNA as had been suggested by theoretical considerations and may have important implications for its immunologic behavior in SLE and perhaps other disorders. (J. Clin. Invest. 1990.86:69-74.)

Association of a four–amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus: Molecular and functional analysis

“…Recent reports suggest that proteins that are degenerated during apoptosis are the source of the autoantigens frequently found in SLE (42)(43)(44)(45). Moreover, autoantigens generated in the process of apoptosis were shown to react with autoantibodies, thereby leading to the tissue deposition of immune complexes and tissue damage (46). EPEPϩ HS1 transmits an accelerated signal through BCR, as demonstrated in the WEHI-231 transfection system (Figure 2).…”

Nucleosome, the Main Autoantigen in Systemic Lupus Erythematosus, Induces Direct Dendritic Cell Activation via a MyD88-Independent Pathway: Consequences on Inflammation

“…Erythematosus, Induces Direct Dendritic Cell Activation via a MyD88-Independent Pathway: Consequences on Inflammation 1 S ystemic lupus erythematosus (SLE) 3 is an inflammatory autoimmune disease of unknown etiology that is characterized by a large amount of circulating autoantibodies with diverse specificities. Among the targets recognized by these autoantibodies is the nucleosome, a complex composed of 180 bp of DNA and the five histone molecules (H1, H2A, H2B, H3, and H4).…”

Aberrant HS1 molecule in a patient with systemic lupus erythematosus

“…[47][48][49][50] Moreover, autoantigens from apoptotic bodies were proven to react with autoantibodies, resulting in the tissue deposition of immune complex. 51 These findings suggest that apoptotic bodies serve as reservoirs of autoantigens in SLE. As shown in WEHI-231 cells, HS1 Dexon A transmits accelerated signal(s) from BCR, which results in increased cell death in immature B lymphocytes ( Figure 5).…”