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 F(1) 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.