PATHOGENIC ANTI-DNA IDIOTYPE-REACTIVE IGG IN INTRAVENOUS IMMUNOGLOBULIN PREPARATIONS

This study was addressed to explore the reactivity of natural anti-idi otypes from commercial lots of immunoglobulins to several idiotypes (I ds), usually expressed by anti-DNA molecules in lupus nephritis. Eleve n intravenous immunoglobulin (IVIG) preparations and nine (three polyv alent and six hyper-immune) intramuscular IgG were investigated for sp ecific content of anti-DNA, anti-F(ab')(2) and antibodies reacting wit h several anti-DNA IgG Ids. Two samples (nos 6 and 11) showed high rea ctivity with allogeneic F(ab')2 and with F(ab')(2) of myeloma proteins bearing the anti-DNA Id 31(+) and the 8.12(+). Since both 31 and 8.12 Id markers are known to characterize pathogenic anti-DNA IgG in syste mic lupus erythematosus (SLE), anti-Id antibodies to these markers wer e obtained by absorbing the IVIG samples nos 6 and 11 to Sepharose col umns coupled with pooled F(ab')(2) fragments of 3I(+)-F4(+)-8.12(+)-my eloma proteins. Inhibition experiments showed that anti-8.12 Id-eluted IgG induced a selective suppression of the DNA-reactive antibodies de rived from patients with active lupus nephritis to their substrate, su ggesting the involvement of 8.12(+) molecules in the SLE glomerular da mage. Since 8.12(+) anti-DNA are nephritogenic antibodies, the occurre nce of anti-8.12(+) Id in commercial IVIG may be of potential therapeu tic relevance in modulating the pathogenic SLE Id network. Previous va riable results of IVIG treatment in SLE, such as resolution of protein uria or worsening nephritis, could be related to variable enrichment o f different lots of IVIG in suppressive anti-pathogenic Id antibodies.