The detection of a common idiotype of anti-DNA antibodies in the sera of patients with monoclonal gammopathies

Abstract

The sera of 265 patients with monoclonal gammopathies were examined for the presence of a dominant idiotype of the anti-DNA antibody [16/6 idiotype (Id)] and for anti-DNA activity. An enzyme-linked immunosorbent assay (ELISA) with a rabbit anti-16/6 antibody revealed 23 (8.7%) sera that contained increased concentrations of the idiotype. Seven of the patients had benign monoclonal gammopathy, three multiple myeloma, three Waldenström macroglobulinemia, five essential mixed cryoglobulinemia, and five monoclonal cryoglobulinemia. In 5 of the 23 sera, antinuclear activity was also noted. In 11 of the 16/6 Id-positive sera the anti-nucleic acid antibody reactions were found to be polyspecific, reacting with polydeoxythymidilic acid and polyinosinic acid, in addition to single-stranded DNA and double-stranded DNA. Similar results were achieved with the purified serum monoclonal components. The specificity of the idiotype analysis was demonstrated with an unrelated dominant idiotype of anti-HBsAg antibody. In none of the patients, except one (with essential mixed cryoglobulinemia), was lupus symptomatology noted.

Pathogenic natural anti-cardiolipin antibodies: the experience from monoclonal gammopathy

“…If the immunoglobulin has autoreactive characteristics it may be regarded as a natural autoantibody. Most of the patients with MG are asymptomatic in relation to the binding specificities of the monoclonal immunoglobulin [26][27][28][29][30]40], although in a few cases the ligand binding characteristics may have clinical impact [41.42]. One of the reasons for the lack of autoimmune manifestations in such patients, as well as in other conditions with high titres of autoantibodies, e.g.…”

“…The autoantibodies recorded among palients with MG, while not associated with respective overt clinical manifestations, may be regarded as an incidental expansion of natural autoantibodies [25][26][27][28][29][30].…”

Antigen inhibition of the interaction between murine monoclonal anti-idiotypic antibodies and human monoclonal anti-DNA antibodies.

“…However, the nature of Id determinants on anti-DNA autoantibodies have not been well characterized since the antigenic sites recognized by anti-Id antibodies have not been clarified in these reports (Isenberg et al 1985;Datta et al 1986 ;Shoenfeld et al 1986). We have described two kinds of murine monoclonal anti-Id antibodies to human monoclonal anti-DNA antibodies (Tamate et al 1986).…”

“…Therefore, analysis of Id in anti-DNA antibodies, which are known to play an important role in the pathogenesis of systemic lupus erythematosus (SLE), may throw some light in the study of the mechanism of autoantibody production. Recently, human monoclonal and serum anti-DNA antibodies were proved to share common cross-reactive idiotypes (CRI) (Hahn and Ebling 1984;Isenberg et al 1984; Shoenfeld et al 1986). CRI of anti-DNA antibodies appear to be widely spread not only among anti-DNA antibodies but also in the antibodies without DNA-binding ability (Isenberg et al 1985 ;Datta et al 1986;Shoenfeld et al 1986).…”

“…Recently, human monoclonal and serum anti-DNA antibodies were proved to share common cross-reactive idiotypes (CRI) (Hahn and Ebling 1984;Isenberg et al 1984; Shoenfeld et al 1986). CRI of anti-DNA antibodies appear to be widely spread not only among anti-DNA antibodies but also in the antibodies without DNA-binding ability (Isenberg et al 1985 ;Datta et al 1986;Shoenfeld et al 1986). These observations should be taken into consideration to understand the Id network regulation on autoantibody production (Jerne 1974;…”