Toward molecular targeting with specific intravenous immunoglobulin preparation.
Intravenous immunoglobulin (IVIg) is used successfully for therapy of inflammatory and autoimmune diseases, especially in cases of conventional therapy resistance. Within the broad spectrum of immunoregulatory activities of IVIg in vitro and in vivo, the anti-idiotypic activity neutralizing the related idiotypes is one of the main mechanisms. Furthermore, IVIg addresses integrins associated with inflammation and immune response thrombosis, such as the RGD (Arg-Gly-Asp) motif, expressed on a large number of cell surface and matrix proteins. In addition, during the last years, anti-Fas activity of IVIg was reported. We fractionated IVIg specific preparation (sIVIg) based on the multispecificities of the IVIg compound. We have generated an IVIg fraction that will show specific activity for lupus idiotypes in vitro. In NZBxW.F1 mice, results showed 200 times more beneficial effect. Using a peptide phage display library technology, we have identified a panel of lupus-related synthetic idiotypes that are mimetics of the idiotypes presented in patients with systemic lupus erythematosus. A column composed of these synthetic lupus-related idiotypes was used to prepare a large amount lupus-specific IVIg. Using the same approach, we prepared anti-anti-beta-2-glycoprotein-I (beta2GPI) specific IVIg for antiphospholipid syndrome (APS). This APS-specific IVIg reduced the fetal loss induced by anti-beta2GPI antibodies by improving the implantation process in a mouse model. Others prepared specific preparations of IVIg to RGD or for Fas. The molecular targeting with specific IVIg may be used for therapeutical purposes, using a smaller amount of IVIg, and targeting more specifically autoimmune diseases, thrombosis, or inflammatory condition.
Blank
Miri
M
Department of Medicine B and The Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.
Nur
Israel
I
Toub
Orgad
O
Maor
Anabel
A
Shoenfeld
Yehuda
Y
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000627:therapeutic use*; D016736:Antiphospholipid Syndrome / Q000188:drug therapy / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000737:chemistry* / Q000276:immunology* / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D009842:Oligopeptides / Q000276:immunology; D019151:Peptide Library; D048069:Tumor Necrosis Factors / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D016756:Immunoglobulins, Intravenous; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D019151:Peptide Library; D048069:Tumor Necrosis Factors; C047981:arginyl-glycyl-aspartic acid