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 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.
Shoenfeld
Yehuda
Y
Department of Internal Medicine B, Sheba Medical Center, Tel Hashomer 52621, Israel. shoenfel@sheba.health.gov.il
Rauova
Lubica
L
Gilburd
Boris
B
Kvapil
Filip
F
Goldberg
Iris
I
Kopolovic
Jury
J
Rovensky
Jozef
J
Blank
Miri
M
D000818:Animals; D004247:DNA / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB
D016756:Immunoglobulins, Intravenous; D004247:DNA