Deficient expression of antibodies specific for bacterial DNA by patients with systemic lupus erythematosus

Antibodies to DNA occur commonly in the sera of normal human subjects and bind to nonconserved sites exclusive to DNA from certain bacterial species. These antibodies are primarily IgG2 and differ from anti-DNA antibodies in systemic lupus erythematosus (SLE) sera, which are primarily IgG1 and bind conserved sites on all DNA. To investigate the immune response to bacterial DNA in SLE, antibodies to single-stranded DNA from Micrococcus lysodeikticus (MC) were measured in normal human subjects and in SLE sera by enzyme-linked immunosorbent assay either directly or following absorption by cellulose bearing calf thymus (CT) DNA; isotype-specific reagents were used to assess the IgG2 response. In these assays, SLE sera had a marked deficiency in antibodies specific for MC single-stranded DNA as demonstrated by the reduction of antibody levels by CT DNA cellulose absorption. Furthermore, IgG2 anti-DNA in SLE sera were cross-reactive with MC and CT single-stranded DNA, whereas IgG2 anti-DNA in normal human subjects' sera were specific for the bacterial DNA antigen. Together, these findings indicate that SLE patients have a marked deficiency in the production of antibodies specific for bacterial DNA antigen. This deficiency could predispose to anti-DNA autoantibody production and result from tolerance defects that distort the array of specificities in the B-cell repertoire.