Enhanced binding of lupus sera to the polyamine‐induced left‐handed z‐dna form of polynucleotides

Abstract

The natural polyamines putrescine, spermidine, and spermine are small polyvalent cations present in all living cells. Spermidine and spermine are excellent promoters of left-handed Z-DNA, an immunogenic form of DNA that binds readily with anti-DNA antibodies in the sera of patients with systemic lupus erythematosus (SLE). We studied the binding of a panel of 16 SLE sera to poly(dA-dC).poly(dG-dT) and poly(dG-m5dC).poly (dG-mSdC) in 'the presence and absence of spermidine and spermine using an enzyme-linked immunosorbent assay. The majority of SLE sera showed a 5&150% mean increase in optical density values when incubated with the polynucleotides and either 0.25 mM spermidine or 0.025 mM spermine than when incubated with the polynucleotides alone. Under these conditions, the polynucleotides assumed the Z-DNA form. Since polyamines are ubiquitous cellular components and since potential

Polyamine induced Z‐conformation of native calf thymus DNA

“…Elevated polyamine levels have been observed in biological fluids of diseased states such as cancer, sickle cell anemia, cystic fibrosis and psoriasis [6]. One of the changes which has received the attention of researchers is the polyamine-induced left-handed Z-conformation of alternating purine-pyrimidine sequences in synthetic polymers or plasmids [6][7][8]. The complex formation between poly(dA-dC).poly-(dG-dT) and polyamines induces Z-conformation which significantly altered the immunogenicity of this polymer and produced anti-Z-DNA antibodies when challenged in experimental animals [9].…”

Interactions of anti-DNA antibodies with Z-DNA

“…Several reports have indicated enhanced binding of SLE sera to left-handed Z-form of DNA polymers [6][7][8], This binding has been considered specific as dsDNA in the B-form has been found to have little or no effect on the Z-DNA binding ability of sera or purified antibodies. Proteins from several other sources have also been observed to display a similar characteristic in their binding to Z-DNA [13][14][15][16].…”

“…Binding to Z-DNA probe (Brpoly (dG-dC)) was carried out as described in Materials and Methods, in the presence of 100 mM NaCI, Biol A and biol B represent anlibody binding lo the Z-DNA probe in ihe absence of any competitor, and in the presence of cardiolipin (500/ig/ml), respectively. desirable in defining the specificity of this antibody for Z-DNA, Despite the lack of evidence to establish unequivocally the presence of a specific anti-Z-DNA autoantibody., the pathological importance of anti-Z-DNA antibodies in SLE has continued to be stressed [6][7][8].…”

“…polyamines spermidine and spermine) have been shown to promote the Z-conformation of polynucleotides [6]. Enhanced binding of SLE sera to DNA conformations altered by these factors has led to the suggestion that these factors may play a pathogenic role in SLE [6][7][8]. Since Z-DNA is highly immunogenie [9,10].…”

Diversity and origin of rheumatologic autoantibodies

“…Unique DNA Conformations One of the more recently described forms of DNA, left-handed or Z DNA, has been shown to be an autoantigen that reacts with both SRD and murine systemic lupus erythematosus (SLE) sera (73,114,128 Heix-turn-Helix DNA with the general structure poly(dG-dC)5dT4, "dumbbell" structures with the general structure dT4(dG-dC)5dT4, and cruciform DNA. The importance and relevance of these studies are based on observations that these unique DNA structures are relatively nuclease resistant and similar nuclease-resistant nucleic acids are highly immunogenic (13).…”