Cross-reactivity distinguishes serum and nephritogenic anti-DNA antibodies in human lupus from their natural counterparts in normal serum.
To distinguish the properties of anti-DNA antibodies in patients with lupus from those in normal individuals, we compared the ligand binding, idiotypic and charge properties of serum anti-DNA antibodies derived from: patients with active lupus; normal individuals; and among Ig eluted from the kidneys of two patients with active lupus nephritis (one with mesangial proliferation and the other with membranous nephropathy). The kidney eluate anti-DNA antibodies were the most cross-reactive; they cross-reacted with ssDNA, poly(GdC), poly(dT), poly(dG), poly(dC), ZDNA, SmRNP and the phospholipids cardiolipin and phosphatidyl serine. Lupus serum anti-DNA antibody cross-reacted with polynucleotides but not with phospholipids, whereas anti-DNA antibodies derived from normal serum reacted only with poly(dT). An anti-idiotype (anti-IdD; produced against serum anti-DNA antibodies from one patient) reacted with: anti-DNA antibodies in 8/9 lupus sera; antibodies in both kidney eluates; and anti-DNA antibodies from 5/7 normal sera. Anti-IdD did not react with Ig that did not bind to DNA. Isoelectric focusing of Ig showed that the charge of anti-DNA antibodies from lupus serum and normal serum were similar and unrestricted (pI 5.4-9.0); Ig in kidney eluates varied: membranous lupus pI 4.5-8.6; mesangial lupus pI 8.1-9.1. We conclude that idiotypically related anti-DNA antibodies in tissue lesions, lupus serum and normal serum from different individuals can be distinguished on the basis of their cross-reactive antigen-binding properties. Furthermore the cross-reactive properties of lupus auto-antibodies may influence their capacity to form glomerular immune deposits.
Sabbaga
J
J
Department of Medicine, Tufts University School of Medicine, Boston, MA.
Pankewycz
O G
OG
Lufft
V
V
Schwartz
R S
RS
Madaio
M P
MP
D000328:Adult; D000974:Antibodies, Antinuclear / Q000032:analysis* / Q000302:isolation & purification; D003429:Cross Reactions; D004277:DNA, Single-Stranded / Q000276:immunology*; D005260:Female; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007525:Isoelectric Focusing; D007668:Kidney / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D009392:Nephrectomy
D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded; D007130:Immunoglobulin Idiotypes