Recognition of <em>Porphyromonas gingivalis</em> Gingipain Epitopes by Natural IgM Binding to Malondialdehyde Modified Low-Density Lipoprotein

<div><h3>Objective</h3><p>Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid and protein epitopes on low-density lipoprotein (LDL) and apoptotic cells. We aimed to identify epitopes on periodontal pathogen <em>Porphyromonas gingivalis</em> recognized by natural IgM binding to malondialdehyde (MDA) modified LDL.</p> <h3>Methods and Results</h3><p>Mouse monoclonal IgM (MDmAb) specific for MDA-LDL recognized epitopes on <em>P. gingivalis</em> on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with <em>P. gingivalis</em> induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR^−/− mice with <em>P. gingivalis</em> induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to <em>P. gingivalis</em> fragments identified as arginine-specific gingipain (Rgp) by mass spectrometry. Recombinant domains of Rgp produced in <em>E. coli</em> were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to <em>P. gingivalis</em> were associated with anti-MDA-LDL levels in humans.</p> <h3>Conclusion</h3><p>Gingipain of <em>P. gingivalis</em> is recognized by natural IgM and shares molecular identity with epitopes on MDA-LDL. These findings suggest a role for natural antibodies in the pathogenesis of two related inflammatory diseases, atherosclerosis and periodontitis.</p>