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

Abstract

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 IgGinhibitory 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 Ј ) 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 Ј ) 2 antibodies by adsorption with an affinity column prepared with normal IgG F(ab Ј ) 2 . Unretained IgG bound exclusively to anti-P F(ab Ј ) 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 Ј ) 2 from a healthy adult and SLE patients. They did not bind to F(ab Ј ) 2 fragments prepared from normal IgG or anti-dsDNA. Ribosomal antigens blocked this antiId-Id interaction. Purified anti-Ids inhibited the binding of anti-P F(ab Ј ) 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. ( J. Clin. Invest. 1998. 102:215-222.)

The lack of anti-idiotypic antibodies, not the presence of the corresponding autoantibodies to glutamate decarboxylase, defines type 1 diabetes

“…Autoantibodies to ribosomal P proteins (anti-P) are regarded as specific for patients with systemic lupus erythematosus. Stafford and colleagues (21)(22)(23) demonstrated that in healthy individuals who tested negative for anti-P antibodies by conventional serologic screenings anti-P antibodies were in fact readily detectable after removal of the inhibitory antibodies. Similarly, autoantibodies to the E2 subunit of the pyruvate dehydrogenase complex, thought to be specific to patients with primary biliary cirrhosis, are present but inhibited by anti-Ids in healthy individuals (24).…”

The immunogenicity of humanized and fully human antibodies

“…58,59 However, in spite of these mechanisms, human serum from non-diseased normal donors contains detectable levels of anti-idiotype antibody to a wide variety of autoantibodies. [60][61][62][63][64][65] Anti-idiotype antibodies are akin to anti-drug antibodies against therapeutic mAbs, that is, they are antibodies with specificity for the unique V region of other immunoglobulin molecules. The presence of autoantibodies indicates that the tolerance system is not perfect and in fact, poly-reactivity to autoantigens re-emerges during the somatic hypermutation that takes place during an immune response.…”

Anti–Idiotypic Antibodies to Anti-Pdc–E2 in Primary Biliary Cirrhosis and Normal Subjects

“…38 In the latter instance, the anti-idiotypic antibodies were found to bind to anti-P F(ab) 2 from both lupus patients and healthy adults. 39 Although normal sera contained anti-idiotypic antibody to anti-PDC-E2, such sera failed to inhibit binding between HRP-conjugated anti-PDC-E2 and PDC-E2, suggesting that anti-idiotypic antibodies (Ab2) in normal sera do not react with the paratope, but rather with other regions on the framework of F(ab) 2 (Ab1). Alternatively, the lack of blocking could be explained by a much stronger binding affinity between PDC-E2 and anti-PDC-E2 (Ab1) in PBC serum than between anti-PDC-E2 (Ab1) and anti-idiotypic antibody (Ab2) in normal serum.…”