The potential role of mycoplasmas as autoantigens and immune complexes in chronic vascular pathogenesis

Many chronic degenerative diseases are suspected of resulting from autoimmune (AI) or immune complex (IC) mechanisms of unknown infectious etiology. Mycoplasmas have been associated with autoantibodies and tissue mimicry and with infertility and neonatal disorders, as well as with IC disorders. Their persistent colonization, which is clinically silent and common among healthy females, makes their etiopathogenic mechanisms difficult to assess. Finding the great apes to be colonized with and serologically expressing the human strains of mycoplasmas, as well as the anti-IgG rheumatoid factor (RF), provided us the ideal model of immunologically-related human disorders. In view of the etiopathologic role of IC in experimental vasculitis, especially collagen vascular diseases such as systemic lupus erythromatosus (SLE) with specific deposition on receptor sites of the vascular basement membranes, an investigation of IC's role in fetal and placental vascular disorders was initiated. The IgG-IC fractions isolated from solubilized human synovial and placental tissue extracts on affinity protein-A columns were further purified by pepsinization to minimize nonspecific Fc binding. Mycoplasmal antigens were identified in the F(ab)₂-IC fractions by reacting the electroblots from SDS-PAGE with rabbit antisera to 6 IgG test serovars. Finding mycoplasmal and ureaplasmal antigens associated with the IgG-IC in synovial and placental tissues suggests their pathogenic role in collagen vascular and reproductive disorders of both humans and the great apes. Mycoplasma cells cultured in rabbit-serum-enriched broth bound rabbit IgG as indicated by their specific reaction with goat anti-rabbit IgG. Polyclonal rabbit antisera raised against the mycoplasma cells binding the gnotobiotic rabbit IgG expressed idiotypic antibodies reactive with heterologous mycoplasmas cultured with whole sera but not with gamma-free or fetal bovine sera. Immunoblot analysis of SDS-PAGE fractionated mycoplasmas with the anti-M. pneumoniae rabbit IgG recognized common IgG epitopes in heterologous mycoplasma cells cultures with whole horse serum. These results demonstrate a potential role and pathogenic mechanism of mycoplasmas acting as a ligand, binding and causing conformational changes of IgG that could also apply to other specific tissue proteins. Conformational changes of bound tissue components could produce "altered-self" antigens to initiate a variety of autoimmune disorders in both humans and the great apes.