Anti-DNA autoantibody activity and idiotypic relationships of human monoclonal proteins

Previous studies showed that polyclonal anti-DNA antibodies from patients with systemic lupus erythematosus (SLE) share cross-reactive idiotypes (CRI). In this report, we used human myeloma proteins (HMP), isolated from the serum of patients with multiple myeloma or Waldenström macroglobulinemia, as probes to further explore this idiotypic cross-reactivity. Fourty-four HMP were tested for DNA-binding capacity and for expression of CRI associated with lupus anti-DNA antibodies. Anti-DNA IgG were immunoaffinity purified from the serum of patient TOF with severe SLE. A xenogeneic anti-idiotype antibody to this IgG was raised in rabbit. This anti-idiotype recognized CRI associated with the combining site of anti-DNA IgG from unrelated SLE patients. Using inhibition competitive-immunoassays, we found that these CRI were present on all but one of the DNA-binding HMP. Furthermore, we observed that these CRI were detectable on an IgG2 lambda, a HMP devoid of anti-DNA activity. These findings are in agreement with those previously obtained in similar studies using murine monoclonal anti-DNA antibodies. These converging results suggest that antibodies expressing anti-DNA-related CRI and antibodies exhibiting anti-DNA-binding affinity constitute overlapping molecular subpopulations.