Efficacy of IVIG affinity-purified anti-double-stranded DNA anti-idiotypic antibodies in the treatment of an experimental murine model of systemic lupus erythematosus

Since the idiotypic network is an important mechanism for controlling the immune repertoire, we tested anti-idiotypic modulation employing concentrated specific natural polyclonal anti-double-stranded (ds) DNA anti-idiotypic antibodies obtained from a commercial IVIG in the treatment of experimental systemic lupus erythematosus (SLE). Specific natural polyclonal anti-dsDNA anti-idiotypic antibodies (IVIG-ID) were affinity purified from IVIG on an anti-dsDNA-Sepharose column constructed from anti-dsDNA idiotypes (ID) affinity purified from 55 patients with active SLE. NZB/W F₁ mice were treated i.v. with 3 weekly injections of IVIG-ID (2 mg/kg/injection) or regular IVIG (400 mg/kg/injection) both before (age 8 weeks) and after developing anti-dsDNA antibodies at the age of 21-22 weeks. The IVIG-ID-treated mice showed a decline in the titer of anti-dsDNA antibodies during the treatment, reaching maximum suppression 1 week after the last injection. A significant difference in the proteinuria level in the IVIG-ID-treated group compared to the control group was observed. Immunohistology showed different patterns of IgG deposition, with mesangial and capillary wall deposits in controls and in the IVIG-treated group, but only mesangial deposits in the IVIG-ID-treated group. The survival time of the IVIG-ID-treated group was longer than the IVIG-treated group. Treatment with concentrated specific anti-dsDNA anti-ID prepared from commercial IVIG is more effective in suppressing the humoral reaction and clinical signs of SLE than native IVIG. These results point to the considerable regulatory role of anti-ID in the mechanism of action of IVIG in SLE.