DOI QR코드

DOI QR Code

Robust immunoreactivity of teenager sera against peptide 19 from Porphyromonas gingivalis HSP60

  • Kwon, Eun-Young (Department of Periodontology, Pusan National University School of Dentistry) ;
  • Cha, Gil Sun (Department of Periodontology, Pusan National University School of Dentistry) ;
  • Joo, Ji-Young (Department of Periodontology, Pusan National University School of Dentistry) ;
  • Lee, Ju-Youn (Department of Periodontology, Pusan National University School of Dentistry) ;
  • Choi, Jeomil (Department of Periodontology, Pusan National University School of Dentistry)
  • 투고 : 2017.05.01
  • 심사 : 2017.06.03
  • 발행 : 2017.06.30

초록

Purpose: Epitope spreading is a phenomenon in which distinct subdominant epitopes become major targets of the immune response. Heat shock protein (HSP) 60 from Porphyromonas gingivalis (PgHSP60) and peptide 19 from PgHSP60 (Pep19) are immunodominant epitopes in autoimmune disease patients, including those with periodontitis. It remains unclear whether Pep19 is a dominant epitope in subjects without periodontitis or autoimmune disease. The purpose of this study was to determine the epitope spreading pattern and verify Pep19 as an immunodominant epitope in healthy teenagers using dot immunoblot analysis. The patterns of epitope spreading in age-matched patients with type 1 diabetes mellitus (type 1 DM) and healthy 20- to 29-year old subjects were compared with those of healthy teenagers. Methods: Peptide from PgHSP60, Mycobacterium tuberculosis HSP60 (MtHSP60), and Chlamydia pneumoniae HSP60 (CpHSP60) was synthesized for comparative recognition by sera from healthy subjects and patients with autoimmune disease (type 1 DM). Dot immunoblot analysis against a panel of peptides of PgHSP60 and human HSP60 (HuHSP60) was performed to identify epitope spreading, and a densitometric image analysis was conducted. Results: Of the peptide from PgHSP60, MtHSP60, and CpHSP60, PgHSP60 was the predominant epitope and was most consistently recognized by the serum samples of healthy teenagers. Most sera from healthy subjects and patients with type 1 DM reacted more strongly with PgHSP60 and Pep19 than the other peptides. The relative intensity of antibody reactivity to Pep19 was higher in the type 1 DM group than in the healthy groups. Conclusions: Pep19 is an immunodominant epitope, not only in autoimmune disease patients, but also in healthy young subjects, as evidenced by their robust immunoreactivity. This result suggests that the Pep19-specific immune response may be an initiator that triggers autoimmune diseases.

키워드

참고문헌

  1. Kivity S, Agmon-Levin N, Blank M, Shoenfeld Y. Infections and autoimmunity--friends or foes? Trends Immunol 2009;30:409-14. https://doi.org/10.1016/j.it.2009.05.005
  2. Vanderlugt CL, Begolka WS, Neville KL, Katz-Levy Y, Howard LM, Eagar TN, et al. The functional significance of epitope spreading and its regulation by co-stimulatory molecules. Immunol Rev 1998;164:63-72. https://doi.org/10.1111/j.1600-065X.1998.tb01208.x
  3. Lehmann PV, Forsthuber T, Miller A, Sercarz EE. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 1992;358:155-7. https://doi.org/10.1038/358155a0
  4. Vanderlugt CL, Neville KL, Nikcevich KM, Eagar TN, Bluestone JA, Miller SD. Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis. J Immunol 2000;164:670-8. https://doi.org/10.4049/jimmunol.164.2.670
  5. van Noort JM, Bajramovic JJ, Plomp AC, van Stipdonk MJ. Mistaken self, a novel model that links microbial infections with myelin-directed autoimmunity in multiple sclerosis. J Neuroimmunol 2000;105:46-57. https://doi.org/10.1016/S0165-5728(00)00181-8
  6. Ercolini AM, Miller SD. The role of infections in autoimmune disease. Clin Exp Immunol 2009;155:1-15. https://doi.org/10.1111/j.1365-2249.2008.03834.x
  7. Steinman L. Despite epitope spreading in the pathogenesis of autoimmune disease, highly restricted approaches to immune therapy may still succeed [with a hedge on this bet]. J Autoimmun 2000;14:278-82. https://doi.org/10.1006/jaut.2000.0379
  8. Kurien BT, Scofield RH. Autoimmunity and oxidatively modified autoantigens. Autoimmun Rev 2008;7:567-73. https://doi.org/10.1016/j.autrev.2008.04.019
  9. Vanderlugt CL, Miller SD. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2002;2:85-95. https://doi.org/10.1038/nri724
  10. Tabeta K, Yamazaki K, Hotokezaka H, Yoshie H, Hara K. Elevated humoral immune response to heat shock protein 60 (hsp60) family in periodontitis patients. Clin Exp Immunol 2000;120:285-93. https://doi.org/10.1046/j.1365-2249.2000.01216.x
  11. Choi J, Lee SY, Kim K, Choi BK. Identification of immunoreactive epitopes of the Porphyromonas gingivalis heat shock protein in periodontitis and atherosclerosis. J Periodontal Res 2011;46:240-5. https://doi.org/10.1111/j.1600-0765.2010.01339.x
  12. Jeong E, Lee JY, Kim SJ, Choi J. Predominant immunoreactivity of Porphyromonas gingivalis heat shock protein in autoimmune diseases. J Periodontal Res 2012;47:811-6. https://doi.org/10.1111/j.1600-0765.2012.01501.x
  13. Kwon EY, Cha GS, Jeong E, Lee JY, Kim SJ, Surh CD, et al. Pep19 drives epitope spreading in periodontitis and periodontitis-associated autoimmune diseases. J Periodontal Res 2016;51:381-94. https://doi.org/10.1111/jre.12318
  14. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2012;35 Suppl 1:S64-71. https://doi.org/10.2337/dc12-s064
  15. Joo JY, Cha GS, Chung J, Lee JY, Kim SJ, Choi J. Peptide 19 of Porphyromonas gingivalis heat shock protein is a potent inducer of low-density lipoprotein oxidation. J Periodontol 2017;88:e58-64. https://doi.org/10.1902/jop.2016.160402
  16. Yu M, Johnson JM, Tuohy VK. A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: a basis for peptide-specific therapy after onset of clinical disease. J Exp Med 1996;183:1777-88. https://doi.org/10.1084/jem.183.4.1777
  17. Kamphuis S, Albani S, Prakken BJ. Heat-shock protein 60 as a tool for novel therapeutic strategies that target the induction of regulatory T cells in human arthritis. Expert Opin Biol Ther 2006;6:579-89. https://doi.org/10.1517/14712598.6.6.579
  18. Sfriso P, Ghirardello A, Botsios C, Tonon M, Zen M, Bassi N, et al. Infections and autoimmunity: the multifaceted relationship. J Leukoc Biol 2010;87:385-95. https://doi.org/10.1189/jlb.0709517

피인용 문헌

  1. Atheroprotective nasal immunization with a heat shock protein 60 peptide from Porphyromonas gingivalis vol.50, pp.3, 2020, https://doi.org/10.5051/jpis.2020.50.3.159
  2. Heat shock protein 60 and cardiovascular diseases: An intricate love‐hate story vol.41, pp.1, 2017, https://doi.org/10.1002/med.21723