Anti-CD40 ligand antibody treatment prevents the development of lupus-like nephritis in a subset of New Zealand black x New Zealand white mice. Response correlates with the absence of an anti-antibody response.
Systemic lupus erythematosus is characterized by B cell production of pathogenic autoantibodies dependent upon cooperation from CD4+ Th cells. The interaction between CD40 on B cells and CD40 ligand (CD40L) on Th cells is necessary for normal thymus-dependent Ab production. An anti-murine CD40L mAb blocks binding of CD40L to CD40 and prevents primary and secondary immune responses to thymus-dependent Ags. In this study, New Zealand Black x New Zealand White lupus-prone mice treated with this anti-CD40L Ab from ages 4 to 10 mo had reduced anti-DNA autoantibody production and renal disease and significantly prolonged survival compared with control mice. Pathologic examination verified the absence of significant renal damage or immune deposition in responding mice. Mice that responded to treatment did not develop an Ab response to the administered Ab. Long-term survivors mounted a substantial Ab response to keyhole limpet hemocyanin after completion of anti-CD40L Ab treatment, suggesting that some of the immunosuppressive effects of the Ab may be reversible. These results suggest a human form of this Ab may have therapeutic utility in human systemic lupus erythematosus.
Early
G S
GS
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03768, USA.
Zhao
W
W
Burns
C M
CM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D006224:Cricetinae; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007668:Kidney / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D023201:CD40 Ligand