Monoclonal antibody to MALA-2 (ICAM-1) reduces acute autoimmune nephritis in kdkd mice.

Hereditary tubulointerstitial nephritis is a prominent cause of renal failure in humans. A variety of animal models utilizing immunologically induced nephritis have been developed. The kdkd congenic variant of the CBA/Ca mouse has normal kidneys at birth but develops progressive, lethal autoimmune nephritis beginning at approximately Week 8. The destruction of renal tubular epithelium in mediated by a population of antigen-specific, H-2Kk-restricted, Lyt-2+, L3T4- T cells. The present experiments demonstrate that systemic treatment with anti-ICAM-1 monoclonal antibody reduces kidney disease in kdkd mice. Anti-ICAM-1 mab localizes to inflammatory sites in the kidney and effects a significant reduction in leukocyte infiltration. Concomitantly, urine protein levels of anti-ICAM-1-treated mice are significantly reduced. The use of anti-adhesion molecule monoclonal antibodies that alter leukocyte activity and/or trafficking may be useful therapies for certain autoimmune disorders.