INTRAVENOUS IMMUNE GLOBULIN THERAPY OF LUPUS NEPHRITIS - USE OF PATHOGENIC ANTI-DNA-REACTIVE IGG

The authors have recently shown that antibodies with anti-idiotype (Id ) specificity to pathogenic Ids of lupus nephritis may occasionally oc cur in several intravenous immune globulin (IVIG) preparations because they are present in healthy donors and the healthy relatives of SLE p atients. In the present study, the authors purified these anti-Ids and treated two SLE patients with nephritis in parallel with conventional high-dose IVIG management with a commercial preparation (IVIG 6) in t hree controls for two months. Because pathogenic Ids of anti-DNA molec ules, such as both 8.12 and F4 Ids, show a cationic mobility in isoele ctric focusing, a commercial preparation of IVIG (11) was absorbed on a Sepharose column coupled with DC-305-39 myeloma protein, namely a 8. 12(+) and F4(+) cationic IgG. Infusion of the eluate (EL-11) induced a prompt resolution of proteinuria levels and an evident decrease of se rum levels of anti-DNA antibodies in both patients, whereas in the thr ee controls, proteinuria and anti-DNA antibodies were scarcely reduced . In addition, plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha were also significantly influenced by both treatme nts. The mean values of both cytokines increased significantly after 1 h and then progressively declined over the next 48 h. It was of inter est, however, that the increased TNF-alpha in the two EL-11-treated pa tients was significantly lower than in the three controls. The data su ggest that reduction of active lupus nephritis by enriched specific an ti-Id molecules is the result of two (or perhaps more) mechanisms: sup pression of pathogenic idiotypes at the cellular level and improvement in the mesangium of the secretion of anti-inflammatory cytokines, suc h as IL-6, whose defective function is related to the autoimmune disor der.