Evidence that a putative anti-idiotypic monoclonal antibody may actually be recognizing circulating immune complexes

Murine monoclonal antibodies (mAb) reacting with affinity-purified antihistone antibodies (AHA) from serum of a patient with systemic lupus erythematosus (SLE) were obtained. One of them, 8B3, was initially considered to recognize idiotypic (Id) determinants in AHA since (a) it reacted with AHA but not with control IgG; (b) this reactivity could be inhibited using affinity-purified AHA, but not with control IgG or whole serum; (c) affinity-isolated 8B3+ antibodies showed antihistone activity and not other activities tested so far; (d) antihistone activity due to 8B3+, but not that of 8B3- from the same serum, could be fully inhibited by the presence of 8B3 mAb in the antihistone assay and (e) serum levels of 8B3 reactivity were higher than normal in SLE patients with AHA (56%), in contrast with SLE patients without AHA (6%). From these results it was deduced that 8B3 defined a cross-reactive Id shared by a subset of AHA in SLE patients. However, the present results suggest that (a) 8B3 mAb did not recognize AHA or Ig, but did recognize a 55 kDa histone-binding protein; (b) this 55 kDa protein was present free at low concentration in all human sera, but also associated with IgG in 8B3+ SLE sera and (c) these complexes are responsible for the false positive results in the antihistone assay as shown for DNA/anti-DNA complexes. Thus, mAbs recognizing the non-Ig moiety of circulating immune complexes may resemble anti-Id antibodies with features of the so-called epibodies. These immune complexes may be responsible for false positive results and caution should be exercised in the interpretation of results.