Immunochemical similarities between monoclonal antibacterial Waldenstrom's macroglobulins and monoclonal anti-DNA lupus autoantibodies.

Abstract

Six monoclonal IgM from patients with Waldenstrom's macroglobulinemia that react with Klebsiella polysaccharides were tested for their ability to bind to nucleic acid antigens. One of the macroglobulins bound to the polynucleotide poly(G), and one bound to poly(G), poly(I), and single-stranded DNA. The reaction with the polynucleotides was specifically inhibited by the Klebsiella polysaccharide K30. A monoclonal lupus anti-DNA antibody (16/6) was found to react weakly with the Klebsiella polysaccharides K30 and K21. Five of the Waldenstrom macroglobulins shared an idiotypic determinant with the 16/6 anti-DNA antibody. The reaction between the macroglobulins and the antiidiotype serum was specifically inhibited by Klebsiella polysaccharides, an indication that the idiotypic marker was in the antigen-binding site of the macroglobulins. These results indicate the existence of widely dispersed conserved variable region genes that encode idiotypically related immunoglobulins with the capacity to bind to both bacterial polysaccharides and nucleic acids. Such genes can be expressed by patients with either Waldenstrom's macroglobulinemia or systemic lupus erythematosus.

Immunochemical Properties of Anti-DNA Antibodies in the Sera of Patients with <i>Escherichia col</i><i>i</i> Bacteremia

“…Indeed, anti-DNA has now been linked to infec tion with bacteria [11][12][13], mycobacteria [14], viruses [15,16], as well as parasites in mice, rabbits, and man [17][18][19], Whether any of these infections contribute directly to SLE has not yet been determined, although a causal role of in fection in SLE would suggest that lupus is mechanistically similar to other autoimmune dieseases where foreign anti gens are clearly provocative. Further studies on the struc tural properties of anti-DNA antibodies arising in lupus and infection are in progress and should clarify these etiological relationships.…”

Antibodies elicited by pneumococcal antigens bear an anti-DNA--associated idiotype.

“…Idiotypic studies have demonstrated a relationship between autoantibodies and antibodies against foreign antigen (1)(2)(3)(4). These studies have led to the hypothesis that there is a genetic relationship between autoantibodies and antibodies to foreign antigens, with the same immunoglobulin variable region genes encoding both pathogenic and protective antibodies.…”

Binding of Monoclonal IgM Rheumatoid Factor to Streptococci via the Antibody Combining Site

“…Naparstek et al [18] found a double specificity of antibodies, which react with both autoantigens and bacterial antigens. Thus, some Waldenstrom macroglobulins with anU-Klebsiella ac tivity share idiotypic determinants with the lupus anti-DNA autoantibody and also bound to nucleic acid antigens.…”