title: Recognition of Porphyromonas gingivalis gingipain epitopes by natural IgM binding to malondialdehyde modified low-density lipoprotein.
abstract: OBJECTIVE
  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 Porphyromonas gingivalis recognized by natural IgM binding to malondialdehyde (MDA) modified LDL.
  
  
  RESULTS
  Mouse monoclonal IgM (MDmAb) specific for MDA-LDL recognized epitopes on P. gingivalis on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR(-/-) mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to P. gingivalis fragments identified as arginine-specific gingipain (Rgp) by mass spectrometry. Recombinant domains of Rgp produced in E. coli were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to P. gingivalis were associated with anti-MDA-LDL levels in humans.
  
  
  CONCLUSIONS
  Gingipain of P. gingivalis 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.
authors.affiliation: Department of Medical Microbiology and Immunology, Institute of Diagnostics, University of Oulu, Oulu, Finland.
authors.forename: S Pauliina
authors.initials: SP
authors.lastname: Turunen
authors.forename: Outi
authors.initials: O
authors.lastname: Kummu
authors.forename: Kirsi
authors.initials: K
authors.lastname: Harila
authors.forename: Marja
authors.initials: M
authors.lastname: Veneskoski
authors.forename: Rabah
authors.initials: R
authors.lastname: Soliymani
authors.forename: Marc
authors.initials: M
authors.lastname: Baumann
authors.forename: Pirkko J
authors.initials: PJ
authors.lastname: Pussinen
authors.forename: Sohvi
authors.initials: S
authors.lastname: Hörkkö
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D001011:Aorta / Q000737:chemistry; D017209:Apoptosis / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D000080867:Gingipain Cysteine Endopeptidases; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D008055:Lipids / Q000032:analysis; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008315:Malondialdehyde / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D016966:Porphyromonas gingivalis / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D000939:Epitopes; D000080867:Gingipain Cysteine Endopeptidases; D007075:Immunoglobulin M; D008055:Lipids; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D003546:Cysteine Endopeptidases