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

Abstract

There is evidence in both murine and human lupus that the production ofanti-DNA antibodies may be triggered by environmental antigens. To explore this further, we studied the serum of 10 nonautoimmune individuals immunized with a polyvalent pneumococcal polysaccharide vaccine. All 10 patients showed a rise in the titer of antipneumococcal antibodies bearing an anti-DNA-associated idiotype. The antipneumococcal response was specific as no idiotypic antitetanus antibodies were detected. Furthermore, no anti-DNA antibodies were present in postvaccination sera. The molecular analysis of antipneumococcal and anti-DNA antibodies bearing a common idiotype will help elucidate how foreign antigen might lead to the production of anti-DNA antibodies in susceptible individuals. (J. Clin.

Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus‐derived peptide cause thrombosis and activation of endothelial cells in vivo

“…In support of this model, studies have demonstrated the presence of anti-doublestranded DNA (anti-dsDNA) antibodies in individuals after the onset of microbial infections (55). Furthermore, antiidiotype studies have shown structural similarities between antibacterial and anti-dsDNA antibodies (56)(57)(58). Molecular mimicry has also been studied in rheumatic fever, where there is well-documented crossreactivity between streptococcal M protein and cardiac myosin, and mAb that bind both Streptococcus and myosin and can induce histopathologic alterations in myocytes (59).…”

Restricted immunoglobulin VH usage and VDJ combinations in the human response to Haemophilus influenzae type b capsular polysaccharide. Nucleotide sequences of monospecific anti-Haemophilus antibodies and polyspecific antibodies cross-reacting with self antigens.

“…In humans, autoreactive antibodies are elicited by infection or by LPS-stimulation of normal B cells (67) and in response to infection and thus may be a feature of many normal immune responses. For example, the immune response against both Streptococcus pneumoniae and Klebsiella species is marked by the expression of anti-DNA associated idiotypes (68,69). Hib is a ubiquitous pathogen, and most individuals have acquired protective levels of antiHib PS Ab by 5 yr ofage (22).…”

The double edged sword of the immune response: mutational analysis of a murine anti-pneumococcal, anti-DNA antibody.

“…However, the initial antigenic stimulus for the production of these autoantibodies remains unclear. Several lines of evidence suggest that microbial antigen may be a stimulus for their production: ( a ) in vitro mutation of an anti-pneumococcal antibody leads to loss of reactivity against pneumococcal antigen, and gain of specificity for dsDNA (13); ( b ) autoimmune NZB mice bred in germ-free conditions and not exposed to environmental microbes have greatly attenuated disease (14); ( c ) protective anti-bacterial antibodies and anti-dsDNA antibodies share idiotypic specificities (15); ( d ) patients with bacterial infection will have transiently elevated titers of anti-dsDNA antibodies that are idiotypically related to the anti-DNA antibodies of patients with SLE (16); and ( e ) cross-reactive antibodies binding both bacterial antigen and dsDNA can be isolated from both humans (17) and mice (18). Some of these cross-reactive antibodies binding both phosphorylcholine (PC), a dominant hapten on the pneumococcal cell wall, and dsDNA, can be protective against a bacterial challenge in vivo, but are also pathogenic and deposit in the kidney (18).…”