Clinical Oral Investigations

, Volume 18, Issue 7, pp 1835–1843 | Cite as

T helper cells from aggressive periodontitis patients produce higher levels of interleukin-1 beta and interleukin-6 in interaction with Porphyromonas gingivalis

  • Jose Roberto Gonzales
  • Sabine Groeger
  • Anders Johansson
  • Jörg Meyle
Original Article



In this study, we analyzed the production of Interleukin-1 beta (IL-1β) and IL-6 by activated CD4+ cells obtained from aggressive periodontitis (AgP) patients in comparison with healthy subjects (HC).

Materials and methods

CD4+ cells were automatically separated from lymphocytes obtained from peripheral blood of patients with AgP and healthy controls. Cells were activated for 4, 8, and 24 h with three different stimuli: anti-CD3/anti-CD28, phytohemagglutinin (PHA), and Porphyromonas gingivalis (P. gingivalis) outer membrane protein (OMP). Protein levels were measured in supernatants of activated CD4+ cells by a bead-based immunoassay (CBA). In addition, serum antibodies against P. gingivalis were determined. Data were analyzed using U test (p < 0.05).


T helper cells of AgP patients activated with P. gingivalis OMP produced higher levels of IL-1β and IL-6 in comparison with healthy controls (p < 0.05). Neither the activation with anti-CD3/anti-CD28 nor the activation with PHA showed significantly different production of IL-1β and IL-6 by the cells 25 % of patients and 17 % of controls presented with high serum reactivity to P. gingivalis.


In view of these results, it is possible to conclude that P. gingivalis contributes to the pathogenesis of AgP by inducing high levels of pro-inflammatory cytokines such as IL-1β and IL-6 by peripheral CD4+ T helper cells.

Clinical relevance

In accordance with the clinical parameters and the immunological data, we suggest that full-mouth disinfection with adjunctive systemic antibiotics might be the anti-infectious non-surgical periodontal treatment of choice in this type of patients. Microbiological analyses at the beginning and at the end of the periodontal treatment are recommended. However, it is necessary to verify these data in longitudinal clinical studies.


T cells Aggressive periodontitis Porphyromonas gingivalis Cytokine production 



The authors thank Mrs. Gaby Halley for her technical assistance. The authors received no financial support.

Conflict of interest

The authors declare that there are no conflicts of interest in this study.


  1. 1.
    Meyle J, Gonzales JR (2001) Influences of systemic diseases on periodontitis in children and adolescents. Periodontology 2000(26):92–112CrossRefGoogle Scholar
  2. 2.
    Schenkein HA, Van Dyke TE (1994) Early-onset periodontitis: systemic aspects of etiology and pathogenesis. Periodontology 2000(6):7–25CrossRefGoogle Scholar
  3. 3.
    Socransky SS, Haffajee AD, Smith C, Duff GW (2000) Microbiological parameters associated with IL-1 gene polymorphisms in periodontitis patients. J Clin Periodontol 27:810–818PubMedCrossRefGoogle Scholar
  4. 4.
    Haffajee AD, Cugini MA, Tanner A, Pollack RP, Smith C, Kent RL Jr, Socransky SS (1998) Subgingival microbiota in healthy, well-maintained elder and periodontitis subjects. J Clin Periodontol 25:346–353PubMedCrossRefGoogle Scholar
  5. 5.
    Guyodo H, Meuric V, Le Pottier L, Martin B, Faili A, Pers JO, Bonnaure-Mallet M (2012) Colocalization of Porphyromonas gingivalis with CD4+ T cells in periodontal disease. FEMS Immunol Med Microbiol 64:175–183. doi: 10.1111/j.1574-695X.2011.00877.x PubMedCrossRefGoogle Scholar
  6. 6.
    Califano JV, Chou D, Lewis JP, Rogers JD, Best AM, Schenkein HA (2004) Antibody reactive with Porphyromonas gingivalis hemagglutinin in chronic and generalized aggressive periodontitis. J Periodontal Res 39:263–268. doi: 10.1111/j.1600-0765.2004.00735.x PubMedCrossRefGoogle Scholar
  7. 7.
    Naito M, Hirakawa H, Yamashita A, Ohara N, Shoji M, Yukitake H, Nakayama K, Toh H, Yoshimura F, Kuhara S, Hattori M, Hayashi T, Nakayama K (2008) Determination of the genome sequence of Porphyromonas gingivalis strain ATCC 33277 and genomic comparison with strain W83 revealed extensive genome rearrangements in P. gingivalis. DNA Res: An Int J Rapid Publ Rep Genes Genomes 15:215–225. doi: 10.1093/dnares/dsn013 CrossRefGoogle Scholar
  8. 8.
    Taylor JJ (2010) Cytokine regulation of immune responses to Porphyromonas gingivalis. Periodontology 2000(54):160–194. doi: 10.1111/j.1600-0757.2009.00344.x CrossRefGoogle Scholar
  9. 9.
    Uehara A, Imamura T, Potempa J, Travis J, Takada H (2008) Gingipains from Porphyromonas gingivalis synergistically induce the production of proinflammatory cytokines through protease-activated receptors with Toll-like receptor and NOD1/2 ligands in human monocytic cells. Cell Microbiol 10:1181–1189. doi: 10.1111/j.1462-5822.2008.01119.x PubMedCrossRefGoogle Scholar
  10. 10.
    Darveau RP, Pham TT, Lemley K, Reife RA, Bainbridge BW, Coats SR, Howald WN, Way SS, Hajjar AM (2004) Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4. Infect Immun 72:5041–5051. doi: 10.1128/IAI.72.9.5041-5051.2004 PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Mahanonda R, Pichyangkul S (2007) Toll-like receptors and their role in periodontal health and disease. Periodontology 2000(43):41–55. doi: 10.1111/j.1600-0757.2006.00179.x CrossRefGoogle Scholar
  12. 12.
    Uehara A, Sugawara S, Tamai R, Takada H (2001) Contrasting responses of human gingival and colonic epithelial cells to lipopolysaccharides, lipoteichoic acids and peptidoglycans in the presence of soluble CD14. Med Microbiol Immunol 189:185–192PubMedCrossRefGoogle Scholar
  13. 13.
    Gemmell E, Polak B, Reinhardt RA, Eccleston J, Seymour GJ (1995) Antibody responses of Porphyromonas gingivalis infected gingivitis and periodontitis subjects. Oral Dis 1:63–69PubMedCrossRefGoogle Scholar
  14. 14.
    Gemmell E, Prajaneh S, Grieco DA, Taylor JJ, Seymour GJ (1999) Apoptosis in Porphyromonas gingivalis-specific T-cell lines. Oral Microbiol Immunol 14:331–338PubMedCrossRefGoogle Scholar
  15. 15.
    Gemmell E, Yamazaki K, Seymour GJ (2002) Destructive periodontitis lesions are determined by the nature of the lymphocytic response. Crit Rev Oral Biol Med : An Off Pub Am Assoc Oral Biologists 13:17–34CrossRefGoogle Scholar
  16. 16.
    Nakayama K (2003) Molecular genetics of Porphyromonas gingivalis: gingipains and other virulence factors. Curr Protein Pept Sci 4:389–395PubMedCrossRefGoogle Scholar
  17. 17.
    Nikaido H (1994) Porins and specific diffusion channels in bacterial outer membranes. J Biol Chem 269:3905–3908PubMedGoogle Scholar
  18. 18.
    Nikaido H (1994) Isolation of outer membranes. Methods Enzymol 235:225–234PubMedCrossRefGoogle Scholar
  19. 19.
    Imai M, Murakami Y, Nagano K, Nakamura H, Yoshimura F (2005) Major outer membrane proteins from Porphyromonas gingivalis: strain variation, distribution, and clinical significance in periradicular lesions. Eur J Oral Sci 113:391–399. doi: 10.1111/j.1600-0722.2005.00235.x PubMedCrossRefGoogle Scholar
  20. 20.
    Murakami Y, Imai M, Nakamura H, Yoshimura F (2002) Separation of the outer membrane and identification of major outer membrane proteins from Porphyromonas gingivalis. Eur J Oral Sci 110:157–162PubMedCrossRefGoogle Scholar
  21. 21.
    Murakami Y, Masuda T, Imai M, Iwami J, Nakamura H, Noguchi T, Yoshimura F (2004) Analysis of major virulence factors in Porphyromonas gingivalis under various culture temperatures using specific antibodies. Microbiol Immunol 48:561–569PubMedCrossRefGoogle Scholar
  22. 22.
    Ebersole JL, Cappelli D, Holt SC (2001) Periodontal diseases: to protect or not to protect is the question? Acta Odontol Scand 59:161–166PubMedCrossRefGoogle Scholar
  23. 23.
    Ansel KM, Djuretic I, Tanasa B, Rao A (2006) Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol 24:607–656. doi: 10.1146/annurev.immunol.23.021704.115821 PubMedCrossRefGoogle Scholar
  24. 24.
    Bartova J, Kratka-Opatrna Z, Prochazkova J, Krejsa O, Duskova J, Mrklas L, Tlaskalova H, Cukrowska B (2000) Th1 and Th2 cytokine profile in patients with early onset periodontitis and their healthy siblings. Mediat Inflamm 9:115–120. doi: 10.1080/096293500411587 CrossRefGoogle Scholar
  25. 25.
    Gilmour J, Lavender P (2008) Control of IL-4 expression in T helper 1 and 2 cells. Immunology 124:437–444. doi: 10.1111/j.1365-2567.2008.02845.x PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Gonzales JR, Herrmann JM, Boedeker RH, Francz PI, Biesalski H, Meyle J (2001) Concentration of interleukin-1beta and neutrophil elastase activity in gingival crevicular fluid during experimental gingivitis. J Clin Periodontol 28:544–549PubMedCrossRefGoogle Scholar
  27. 27.
    Preiss DS, Meyle J (1994) Interleukin-1 beta concentration of gingival crevicular fluid. J Periodontol 65:423–428PubMedCrossRefGoogle Scholar
  28. 28.
    Kinane DF, Shiba H, Hart TC (2005) The genetic basis of periodontitis. Periodontology 2000 39:91–117. doi: 10.1111/j.1600-0757.2005.00118.x PubMedCrossRefGoogle Scholar
  29. 29.
    Graves DT, Cochran D (2003) The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 74:391–401. doi: 10.1902/jop.2003.74.3.391 PubMedCrossRefGoogle Scholar
  30. 30.
    Ben-Sasson SZ, Hu-Li J, Quiel J, Cauchetaux S, Ratner M, Shapira I, Dinarello CA, Paul WE (2009) IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A 106:7119–7124. doi: 10.1073/pnas.0902745106 PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Kishimoto T (2005) Interleukin-6: from basic science to medicine—40 years in immunology. Annu Rev Immunol 23:1–21. doi: 10.1146/annurev.immunol.23.021704.115806 PubMedCrossRefGoogle Scholar
  32. 32.
    Neurath MF, Finotto S (2011) IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev 22:83–89. doi: 10.1016/j.cytogfr.2011.02.003 PubMedCrossRefGoogle Scholar
  33. 33.
    Narimatsu M, Maeda H, Itoh S, Atsumi T, Ohtani T, Nishida K, Itoh M, Kamimura D, Park SJ, Mizuno K, Miyazaki J, Hibi M, Ishihara K, Nakajima K, Hirano T (2001) Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells. Mol Cell Biol 21:6615–6625PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Chen CC, Chang KL, Huang JF, Huang JS, Tsai CC (1997) Correlation of interleukin-1 beta, interleukin-6, and periodontitis. Kaohsiung J Med Sci 13:609–617PubMedGoogle Scholar
  35. 35.
    Goutoudi P, Diza E and Arvanitidou M (2012) Effect of periodontal therapy on crevicular fluid interleukin-6 and interleukin-8 levels in chronic periodontitis. Int J Dentistry 2012:362905. doi:  10.1155/2012/362905
  36. 36.
    Robati M, Ranjbari A, Ghafourian Boroujerdnia M, Chinipardaz Z (2011) Detection of IL-4, IL-6 and IL-12 serum levels in generalized aggressive periodontitis. Iran J Immunol: IJI 8:170–175PubMedGoogle Scholar
  37. 37.
    Teles FR, Teles RP, Martin L, Socransky SS, Haffajee AD (2012) Relationships among interleukin-6, tumor necrosis factor-alpha, adipokines, vitamin D, and chronic periodontitis. J Periodontol 83:1183–1191. doi: 10.1902/jop.2011.110346 PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Zhao C, Wu Y, Zhang J, Huang P (2001) Detection of interleukin-6 in gingival crevicular fluid from active and non-active adult periodontitis sites. Hua Xi Yi Ke Da Xue Xue Bao 32:444–445PubMedGoogle Scholar
  39. 39.
    Bozkurt FY, Berker E, Akkus S, Bulut S (2000) Relationship between interleukin-6 levels in gingival crevicular fluid and periodontal status in patients with rheumatoid arthritis and adult periodontitis. J Periodontol 71:1756–1760. doi: 10.1902/jop.2000.71.11.1756 PubMedCrossRefGoogle Scholar
  40. 40.
    Hirahara K, Ghoreschi K, Laurence A, Yang XP, Kanno Y, O’Shea JJ (2010) Signal transduction pathways and transcriptional regulation in Th17 cell differentiation. Cytokine Growth Factor Rev 21:425–434. doi: 10.1016/j.cytogfr.2010.10.006 PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Lee YK, Mukasa R, Hatton RD, Weaver CT (2009) Developmental plasticity of Th17 and Treg cells. Curr Opin Immunol 21:274–280. doi: 10.1016/j.coi.2009.05.021 PubMedCrossRefGoogle Scholar
  42. 42.
    D’Aiuto F, Parkar M, Andreou G, Brett PM, Ready D, Tonetti MS (2004) Periodontitis and atherogenesis: causal association or simple coincidence? J Clin Periodontol 31:402–411. doi: 10.1111/j.1600-051X.2004.00580.x PubMedCrossRefGoogle Scholar
  43. 43.
    Gani DK, Lakshmi D, Krishnan R, Emmadi P (2009) Evaluation of C-reactive protein and interleukin-6 in the peripheral blood of patients with chronic periodontitis. J Indian Soc Periodontol 13:69–74. doi: 10.4103/0972-124X.55840 PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Shimada Y, Komatsu Y, Ikezawa-Suzuki I, Tai H, Sugita N, Yoshie H (2010) The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein. J Periodontol 81:1118–1123. doi: 10.1902/jop.2010.090741 PubMedCrossRefGoogle Scholar
  45. 45.
    Sun XJ, Meng HX, Shi D, Xu L, Zhang L, Chen ZB, Feng XH, Lu RF, Ren XY (2009) Elevation of C-reactive protein and interleukin-6 in plasma of patients with aggressive periodontitis. J Periodontal Res 44:311–316. doi: 10.1111/j.1600-0765.2008.01131.x PubMedCrossRefGoogle Scholar
  46. 46.
    Nibali L, Tonetti MS, Ready D, Parkar M, Brett PM, Donos N, D’Aiuto F (2008) Interleukin-6 polymorphisms are associated with pathogenic bacteria in subjects with periodontitis. J Periodontology 79:677–683. doi: 10.1902/jop.2008.070453 CrossRefGoogle Scholar
  47. 47.
    Kato N, Ohyama H, Nishimura F, Matsushita S, Takashiba S, Murayama Y (2005) Role of helper T cells in the humoral immune responses against 53-kDa outer membrane protein from Porphyromonas gingivalis. Oral Microbiol Immunol 20:112–117. doi: 10.1111/j.1399-302X.2004.00203.x PubMedCrossRefGoogle Scholar
  48. 48.
    Ohyama H, Matsushita S, Kato N, Nishimura F, Oyaizu K, Kokeguchi S, Kurihara H, Takashiba S, Nishimura Y, Murayama Y (1998) T cell responses to 53-kDa outer membrane protein of Porphyromonas gingivalis in humans with early-onset periodontitis. Human immunol 59:635–643CrossRefGoogle Scholar
  49. 49.
    Gonzales JR, Groger S, Boedeker RH, Meyle J (2012) Expression and secretion levels of Th1 and Th2 cytokines in patients with aggressive periodontitis. Clin Oral Investig 16:1463–1473. doi: 10.1007/s00784-011-0634-8 PubMedCrossRefGoogle Scholar
  50. 50.
    Armitage GC (1999) Development of a classification system for periodontal diseases and conditions. Ann Periodontol/Am Acad Periodontol 4:1–6. doi: 10.1902/annals.1999.4.1.1 CrossRefGoogle Scholar
  51. 51.
    Lang NP, Lindhe J, van der Velden U, European Workshop in Periodontology group D (2005) Advances in the prevention of periodontitis. Group D consensus report of the 5th European Workshop in Periodontology. J Clin Periodontol 32(Suppl 6):291–293. doi: 10.1111/j.1600-051X.2005.00825.x PubMedCrossRefGoogle Scholar
  52. 52.
    Gonzales JR, Michel J, Rodriguez EL, Herrmann JM, Bodeker RH, Meyle J (2003) Comparison of interleukin-1 genotypes in two populations with aggressive periodontitis. Eur J Oral Sci 111:395–399PubMedCrossRefGoogle Scholar
  53. 53.
    Nakajima T, Yamazaki K, Sakurai K, Gemmell E, Seymour GJ, Hara K (1998) Detection of clonotypic changes of T cells after stimulation with Porphyromonas gingivalis. Oral Microbiol Immunol 13:238–245PubMedCrossRefGoogle Scholar
  54. 54.
    Bird PS, Gemmell E, Polak B, Paton RG, Sosroseno W, Seymour GJ (1995) Protective immunity to Porphyromonas gingivalis infection in a murine model. J Periodontol 66:351–362PubMedCrossRefGoogle Scholar
  55. 55.
    Aoyagi T, Yamazaki K, Kabasawa-Katoh Y, Nakajima T, Yamashita N, Yoshie H, Hara K (2000) Elevated CTLA-4 expression on CD4 T cells from periodontitis patients stimulated with Porphyromonas gingivalis outer membrane antigen. Clin Exp Immunol 119:280–286PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Boyd J, McBride BC (1984) Fractionation of hemagglutinating and bacterial binding adhesins of Bacteroides gingivalis. Infect Immun 45:403–409PubMedCentralPubMedGoogle Scholar
  57. 57.
    Bougas K, Ransjo M, Johansson A (2012) Effects of Porphyromonas gingivalis surface-associated material on osteoclast formation. Odontol/ Soc Nippon Dental Univ. doi: 10.1007/s10266-012-0068-z Google Scholar
  58. 58.
    Brage M, Holmlund A, Johansson A (2011) Humoral immune response to Aggregatibacter actinomycetemcomitans leukotoxin. J Periodontal Res 46:170–175. doi: 10.1111/j.1600-0765.2010.01325.x PubMedCrossRefGoogle Scholar
  59. 59.
    Pene J, Rahmoun M, Temmerman S, Yssel H (2003) Use of anti-CD3/CD28 mAb coupled magnetic beads permitting subsequent phenotypic analysis of activated human T cells by indirect immunofluorescence. J Immunol Methods 283:59–66PubMedCrossRefGoogle Scholar
  60. 60.
    Trickett A, Kwan YL (2003) T cell stimulation and expansion using anti-CD3/CD28 beads. J Immunol Methods 275:251–255PubMedCrossRefGoogle Scholar
  61. 61.
    Abdalla AO, Kiaii S, Hansson L, Rossmann ED, Jeddi-Tehrani M, Shokri F, Osterborg A, Mellstedt H, Rabbani H (2003) Kinetics of cytokine gene expression in human CD4+ and CD8+ T-lymphocyte subsets using quantitative real-time PCR. Scand J Immunol 58:601–606PubMedCrossRefGoogle Scholar
  62. 62.
    Oda N, Minoguchi K, Tanaka A, Yokoe T, Minoguchi H, Matsuo H, Nakashima M, Tasaki T, Adachi M (2002) Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells. Clin Exp Allergy : J Br Soc Allergy Clin Immunol 32:1782–1786CrossRefGoogle Scholar
  63. 63.
    Bian Y, Hiraoka S, Tomura M, Zhou XY, Yashiro-Ohtani Y, Mori Y, Shimizu J, Ono S, Dunussi-Joannopoulos K, Wolf S, Fujiwara H (2005) The capacity of the natural ligands for CD28 to drive IL-4 expression in naive and antigen-primed CD4+ and CD8+ T cells. Int Immunol 17:73–83. doi: 10.1093/intimm/dxh188 PubMedCrossRefGoogle Scholar
  64. 64.
    Beikler T, Peters U, Prior K, Ehmke B, Flemmig TF (2005) Sequence variations in rgpA and rgpB of Porphyromonas gingivalis in periodontitis. J Periodontal Res 40:193–198. doi: 10.1111/j.1600-0765.2005.00783.x PubMedCrossRefGoogle Scholar
  65. 65.
    Borch TS, Holmstrup P, Bendtzen K, Nielsen CH (2010) In vitro cytokine responses to periodontal pathogens: generalized aggressive periodontitis is associated with increased IL-6 response to Porphyromonas gingivalis. Scand J Immunol 71:440–446. doi: 10.1111/j.1365-3083.2010.02390.x PubMedCrossRefGoogle Scholar
  66. 66.
    Groeger S, Domann E, Gonzales JR, Chakraborty T, Meyle J (2011) B7-H1 and B7-DC receptors of oral squamous carcinoma cells are upregulated by Porphyromonas gingivalis. Immunobiology 216:1302–1310. doi: 10.1016/j.imbio.2011.05.005 PubMedCrossRefGoogle Scholar
  67. 67.
    Becerik S, Ozsan N, Gurkan A, Ozturk VO, Atilla G, Emingil G (2011) Toll like receptor 4 and membrane-bound CD14 expressions in gingivitis, periodontitis and CsA-induced gingival overgrowth. Arch Oral Biol 56:456–465. doi: 10.1016/j.archoralbio.2010.11.008 PubMedCrossRefGoogle Scholar
  68. 68.
    Teles RP, Gursky LC, Faveri M, Rosa EA, Teles FR, Feres M, Socransky SS, Haffajee AD (2010) Relationships between subgingival microbiota and GCF biomarkers in generalized aggressive periodontitis. J Clin Periodontol 37:313–323. doi: 10.1111/j.1600-051X.2010.01534.x PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Kelk P, Claesson R, Chen C, Sjostedt A, Johansson A (2008) IL-1beta secretion induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans is mainly caused by the leukotoxin. Int J Med Microbiol: IJMM 298:529–541. doi: 10.1016/j.ijmm.2007.06.005 PubMedCrossRefGoogle Scholar
  70. 70.
    Kelk P, Abd H, Claesson R, Sandstrom G, Sjostedt A, Johansson A (2011) Cellular and molecular response of human macrophages exposed to Aggregatibacter actinomycetemcomitans leukotoxin. Cell Death Dis 2:e126. doi: 10.1038/cddis.2011.6 PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Havemose-Poulsen A, Sorensen LK, Stoltze K, Bendtzen K, Holmstrup P (2005) Cytokine profiles in peripheral blood and whole blood cell cultures associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis. J Periodontol 76:2276–2285. doi: 10.1902/jop.2005.76.12.2276 PubMedCrossRefGoogle Scholar
  72. 72.
    Brett PM, Zygogianni P, Griffiths GS, Tomaz M, Parkar M, D’Aiuto F, Tonetti M (2005) Functional gene polymorphisms in aggressive and chronic periodontitis. J Dent Res 84:1149–1153PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jose Roberto Gonzales
    • 1
  • Sabine Groeger
    • 1
  • Anders Johansson
    • 2
  • Jörg Meyle
    • 1
  1. 1.Department of PeriodontologyJustus-Liebig University of GiessenGiessenGermany
  2. 2.Molecular Periodontology/OdontologyUniversity of UmeåUmeåSweden

Personalised recommendations