Pathogenic anti-DNA idiotype-reactive IgG in intravenous immunoglobulin preparations

Abstract

SUMMARY This study was addressed to explore the reactivity of natural anti‐idiotypes from commercial lots of immunoglobulins to several idiotypes (Ids), usually expressed by anti‐DNA molecules in lupus nephritis. Eleven intravenous immunoglobulin (IVIG) preparations and nine (three polyvalent and six hyper‐immune) intramuscular IgG were Investigated for specific content of anti‐DNA, anti‐F(ab′)2 and antibodies reacting with several anti‐DNA IgG Ids. Two samples (nos 6 and 11) showed high reactivity 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 systemic lupus erythematosus (SLE), anti‐Id antibodies to these markers were obtained by absorbing the IVIG samples nos 6 and 11 to Sepharose columns coupled with pooled (ab′)2 fragments of 31+‐F4+‐8.12+‐myeloma proteins. Inhibition experiments showed that anti‐8.12 Id‐eluted IgG induced a selective suppression of the DNA‐reactive antibodies derived from patients with active lupus nephritis to their substrate, suggesting the involvement of 8.12+ molecules in the SLE glomerular damage. Since 8.12+ anti‐DNA are nephritogenic antibodies, the occurrence of anti‐8.12+ Id in commercial IVIG may be of potential therapeutic relevance in modulating the pathogenic SLE Id network. Previous variable results of IVIG treatment in SLE, such as resolution of proteinuria or worsening nephritis, could be related to variable enrichment of different lots of IVIG in suppressive anti‐pathogenic Id antibodies.

Autoantibody-Induced Formation of Immune Complexes in Normal Human Serum

“…Anti-factor VIII [72,73] Anti-DNA [74][75][76] Anti-GPIIb/IIIa [77] Anti-thyroglobulin [74,78] Others Complement proteins [79] RGD motif* [80] *Fibronectin, vitronectin, osteopontin, collagens, thrombospondin, fibrinogen, and von Willebrand factor are adhesive proteins containing the tripeptide arginine-glycineaspartic acid (RGD) as their cell recognition site.…”

Intravenous immunoglobulin therapy for autoimmune diseases

“…Anti-Id antibodies are effective in the treatment or prevention of disease manifestations by abrogating the binding of pathogenic auto-antibodies to their corresponding antigen both in vitro [23]and in vivo [24]. IVIg preparations contain antibodies against cytokines including granulocyte-macrophage colony-stimulating factor [25], anti-BAFF (B-cell-activating factor of the TNF family) and anti-APRIL (a proliferationinducing ligand) antibodies [26].…”

The steroid-sparing effect of intravenous immunoglobulin in patients with autoimmune diseases

“…IVIg has an extremely broad spectrum of antigen specificity, including bacteria and viruses, as well as idiotypes [4]. IVIg preparations contain anti-idiotypes against SLE-associated idiotypes (anti-dsDNA and antiphospholipid antibody idiotypes), enabling inhibition of autoantibody binding to their corresponding antigens [52][53][54]. In addition, antiidiotypic antibodies inhibit the spontaneous secretion of antidsDNA antibodies from the blood mononuclear cells of SLE patients [55].…”