CDR molecular localization of possible anti-idiotypic anti-DNA antibodies in normal subjects, patients with SLE, and SLE first-degree relatives.

Patients with active systemic lupus erythematosus (SLE) with disease worsening or severe flares frequently show very low levels of serum immunoglobulin G (IgG) anti-F(ab')2 antibody. Anti-F(ab')2 antibody probably represents a polyclonal collection of generic anti-idiotypic antibodies involved in immune homeostasis. We synthesized the entire variable regions of the heavy and light chains (VH and VL) of two monoclonal anti-DNA antibodies, V88 and 2A4, as overlapping 7-mers on small polypropylene pins and tested these linear segments of anti-DNA V-regions for reactivity against serum samples from 10 normal subjects with high serum IgG anti-F(ab')2, 11 normal subjects with low anti-F(ab')2, 5 patients with SLE with active uncontrolled disease, 3 patients with SLE in remission, and 8 unaffected normal first-degree SLE relatives. VH and VL regions of a human monoclonal IgG anti-rabies antibody were also tested as a control. Concordant IgG antibody reacting with the same complementarity-determining regions (CDRs) was arbitrarily scored as indicative of the presence of anti-idiotypic antibody in test serum samples. Among normal subjects with either high or low serum anti-F(ab')2 levels, 10% to 21% showed strong concordant anti-CDR reactions with either the monoclonal anti-DNA or the control monoclonal anti-rabies V-region sequences. However, all patients with active SLE showed no detectable anti-CDR-reactive antibody. Patients with SLE in remission often showed return of strong concordant anti-CDR antibody. Normal unaffected SLE relatives also showed high levels of anti-CDR reactivity for both monoclonal anti-DNA and anti-rabies antibody sequences.