Treatment of (NZB x NZW)F1 disease with anti-I-A monoclonal antibodies.

(NZB x NZW)F1 mice spontaneously develop an autoimmune syndrome characterized by a fatal immune complex glomerulonephritis. Administration of monoclonal antibodies specific for an I region gene product (I-Az) of the H-2 haplotype associated with susceptibility to glomerulonephritis in these animals produced a remission in female mice with established renal disease. The results demonstrated that anti-I-A therapy stabilized the level of proteinuria and increased the 1-yr survival rate from 10% to greater than 90% in treated animals relative to control mice. These findings may ultimately have therapeutic potential for the treatment of systemic lupus erythematosus.

In vivo effects of antibodies to immune response gene products. I. Haplotype-specific suppression of humoral immune responses with a monoclonal anti-I-A.

Immune response (Ir) gene products control immunologic function at several critical sites. We administered in vivo a monoclonal antibody reactive with I-Ak to F1 mice with the genotype H-2k/b. These treated mnice made a markedly reduced antibody response to antigen (H,G)-A--L, under the control of I-Ak, but not to antigen (T,G)-A--L, under the control of I-Ab. This relative specificity was lost if the antigen was given in complete Freund's adjuvant rather than aqueous solution. The monoclonal antibody reduced the antibody titer in an ongoing, secondary response as well. Several potential mechanisms can be postulated for this effect. This haplotypic specificity might ultimately be relevant to human disease.