Anti-idiotypic antibodies prevent the serologic detection of antiribosomal P autoantibodies in healthy adults.

A subset of SLE patients has serologically detectable autoantibodies to the ribosomal P proteins (anti-P). We reported the discovery of covert anti-P antibodies and their masking IgG-inhibitory antibodies in the sera of healthy adults. The aim of this study was to determine if these IgG-inhibitory antibodies are anti-idiotypic antibodies (anti-Ids). IgG and IgG-depleted fractions of plasma from two healthy adults were assayed for inhibition of anti-P F(ab')2 binding to the ribosomal P proteins in immunoblot. Anti-P antibody activity was completely inhibited by plasma IgG, whereas there was no inhibition by IgG-depleted plasma. IgG-inhibitory antibodies recognized a cross-reactive epitope among anti-P from different SLE patients. Plasma IgG from one healthy adult was depleted of pepsin agglutinators and generic anti-F(ab')2 antibodies by adsorption with an affinity column prepared with normal IgG F(ab')2. Unretained IgG bound exclusively to anti-P F(ab')2 in ELISA. Using four affinity columns, we isolated IgG anti-Ids to anti-P antibodies from four healthy adults. These purified anti-Ids bound to anti-P F(ab')2 from a healthy adult and SLE patients. They did not bind to F(ab')2 fragments prepared from normal IgG or anti-dsDNA. Ribosomal antigens blocked this anti-Id-Id interaction. Purified anti-Ids inhibited the binding of anti-P F(ab')2 from patients to ribosomal P proteins. SLE patients without overt anti-P antibodies also possessed IgG anti-Ids to anti-P antibodies. We conclude that IgG-inhibitory antibodies are anti-Ids to anti-P antibodies, and are directed to public idiotopes on anti-P antibodies. These anti-Ids may be part of an Id network that regulates anti-P antibody expression, and perhaps pathogenicity.