We are using cookies to implement functions like login, shopping cart or language selection for this website. Furthermore we use Google Analytics to create anonymized statistical reports of the usage which creates Cookies too. You will find more information in our privacy policy.
OK, I agree I do not want Google Analytics-Cookies
International Poster Journal of Dentistry and Oral Medicine
Login:
username:

password:

Plattform:

Forgotten password?

Registration

Int Poster J Dent Oral Med 7 (2005), No. 4     15. Dec. 2005

Int Poster J Dent Oral Med 2005, Vol 7 No 04, Poster 293

HLA associations to periodontopathic bacteria

Language: English

Authors:
OA Dr. Stefan Reichert
Universitätspoliklinik für Zahnerhaltungskunde und Parodontologie, Martin-Luther-Universität Halle-Wittenberg

Dr. med. dent. Jamal M. Stein
Klinik für Zahnerhaltung, Parodontologie und Präventive Zahnheilkunde, RWTH Aachen

Univ.-Prof. Dr. Hans-Günter Schaller
Universitätspoliklinik für Zahnerhaltungskunde und Parodontologie, Martin-Luther-Universität Halle-Wittenberg

Dr. rer. nat. Helmut Machulla
Interdisziplinäres HLA Labor, Martin-Luther-Universität Halle-Wittenberg

Date/Event/Venue:
25.-28. August 2004
Joint Meeting of the CED, NOF of the IADR
Istanbul

Introduction

Our previous studies revealed HLA class I- and II-associations to aggressive (AP) and chronic (CP) periodontitis (Machulla et al. 2002, Reichert et al. 2003, Stein et al. 2003). Antigenic peptides were bound by HLA molecules over specific pockets of the hypervariable peptid binding region in order to present them T lymphocytes. In patients with advanced periodontitis, HLA class II-molecules were expressed by Langerhans cells in both oral gingival epithelium and pocket epithelium (Nunes et al. 1994). Colonization of periodontopathic bacteria and antigen specific immune response could be controlled by polymorphism of HLA alleles. That's why an association from HLA to periodontopathic bacteria could be exist.

Fig. 1 (Hjelmström et al. 1996) Presentation of an antigenic peptide through the hypervariable binding groove of a HLA class II molecule (HLA-DQ). The T cell receptor recognises as well as structures of the HLA molecule and bound peptide. The length of the peptides vary from 13-25 amino acids.

Objectives

The goal of the present study was to evaluate HLA associations to A. actinomycetemcomitans (A.a.), P. gingivalis (P.g.), P. intermedia (P.i.), T. forsythensis (T.f.) and T. denticola (T.d.) in patients with both aggressive and chronic periodontitis.

Material and Methods

In both patient groups the smoking status, the approximal plaque index (API), bleeding on probing (BOP), pocket depth (PD), clinical attachment loss in general (CAL) and on the microbial test-sites (CALBact.) were determined. For the microbial assessment subgingival plaque samples were taken from the deepest four pockets (CALBact. > 5 mm) by means of sterile paper points. Bacterial infection was analyzed employing a PCR-rSSO microDent DNA-Strip technique (Hain Lifescience GmbH, Nehren, Germany). HLA-A, -B, -Cw, -DR, -DQ typing was performed by both CDC (Complement Depending Cytotoxicity assay, BAG, Lich, Germany) and polymerase chain reaction with sequence-specific primers (PCR-SSP, GenoVision VertriebsmbH Schwechat, Austria). Statistical calculations were carried out by Chi² testing, with Yates correction or Fishers Exact test, if appropriate. In order to determine the adjusted odds ratio (OR) of certain HLA markers for an infection with one of the periodontopathic bacteria the confounding variables age, gender, nicotine consumption and CALBact. were additional included in a logistic regression model. All patients and controls were of Caucasian descent and were unrelated and free from other general diseases known to be associated with certain HLA markers.

Results

AP patients were in comparison to CP patients significantly younger, more frequently smoker and A.a. positive. CP patients were significantly more infected with T.d. (Table 1).

Variable

Chronic periodontitis (CP)

N = 35

Aggressive periodontitis (AP)

N = 33

P values

AP + CP

N = 68

Median age (range)

47 (27-68)

37 (15-55)

0,0001

42,5 (15-68)

females %

62,9

57,6

0,656

60,0

smoker %

14,3

48,5

0,002

30,9

API % (SD)

62,1 (10,5)

53,5 (34,8)

0,286

58,0 (29,9)

BOP % (SD)

64,4 (28,7)

71,6 (28,7)

0,317

67,8 (28,7)

PD mm (SD)

5,4 (1,2)

5,8 (1,6)

0,212

5,6 (1,4)

CAL mm (SD)

6,1 (1,5)

6,5 (1,9)

0,338

6,3 (1,7)

CAL Bact. (SD)

7,4 (1,8)

7,6 (2,0)

0,613

7,5 (1,9)

A.actinomycetem-comitans (%)

9 (25,7)

16 (48,5)

0,052

25 (36,8)

P. gingivalis (%)

33 (94,3)

26 (78,8)

0,079

59 (86,8)

P. intermedia (%)

22 (62,9)

21 (63,6)

0,947

43 (63,2)

T. forsythensis (%)

34 (97,1)

29 (87,9)

0,191

63 (92,6)

T. denticola (%)

35 (100)

29 (87,9)

0,050

64 (92,1)

Table 1: Demografic and clinical parameters of all investigated cohorts

 

The proof of P.g. was significantly positively correlated with the occurrence of P.i. and T.f.. Both, P.i. and T.f. were positively correlated with the detection of T.d. (Table 2).

 

 

A.a.

P.g.

P.i.

T.f.

T.d.

A.a. r

P

1,000

-,152

,215

,012

,922

-,136

,270

,061

,621

P.g. r

P

-,125

,215

1,000

,242*

,047

,389**

,001

,087

,482

P.i. r

P

,012

,922

,242*

,047

1,000

,136

,270

,328**

,006

T.f. r

P

-,136

,270

,389**

,001

,136

,270

1,000

,408**

,001

T.d. r

P

,016

,621

,087

,482

,328**

,006

,408**

,001

1,000

Table 2: Correlations between the five proved bacteria. *P <0.05, **P < 0.01

 

The occurrence of an A.a. Infection was found to be positively associated with the haplotypes HLA-B*08:Cw*07:DRB1*03:DRB3*(DR52):DQB1*02 and HLA-DRB1*13:DRB3*(DR52):DQB1*06 as well as the HLA-B super-type Bw6. On the other hand a homozygosity for HLA-Bw4 and HLA-DRB1*04:DRB4*(DR53):DQB1*03(DQ7/DQ8) were connected with a reduced risk for an A.a. infection. The HLA markers A*02 and A*23/*24(A9) increased the infection risk for P.g. and the complex P.g., T.f., T.d., respectively. An infection with P.i. occurred less frequent in patients expressing HLA-B*51/*52(B5), HLA-DRB3*(DR52) homozygous and two combinations with HLA-DRB1*13. T.f. was negatively associated with HLA-A*33 (Table 3).

 

HLA-

Number HLA positive patients

Microorganisms

infected patients %

OR

P values

HLA +

HLA-

Bw6

B*08:Cw*07:DRB1*03:DRB3*:DQB1*02

DRB1*13:DRB3*:DQB1*06

Bw4 homozygous

DRB1*04:DRB4*:DQB1*03( DQ7/DQ8 )

55

  8

13

13

11

A.a.

A.a.

A.a.

A.a.

A.a.

43,6

75,0

61,5

  7,7

  9,1

  7,7

31,7

30,9

43,6

42,1

  8,2

  6,2

  4,5

  0,1

  0,2

0,052

0,039

0,029

0,052

0,077

A*02

30

P.g.

P.g., T.f., T.d.

100,0

  93,3

76,3

71,7

*

  5,5

*

0,040

A*23/ A*24 (A9)

14

P.g., T.f., T.d.

100,0

75,9

*

*

B*51 /B*52 (B5)

DRB3*(DR52) homozygous

B*44:DRB1*13

DRB1*13:(DRB3*:DQB1*06) only AP group

  8

  8

  4

  6

P.i.

P.i.

P.i.

P.i.

  25,0

  25,0

   0,0

  16,7

68,3

68,3

67,2

74,1

  0,2

  0,1

     0,001

   0,07

0,030

0,015

0,746

0,024

A*33

  6

T.f.

  66,7

95,2

   0,03

0,025

Table 3: HLA associations to five periodontopathic bacteria. *OR could not be calculated

Conclusions

Single HLA markers, HLA homocygosities and HLA combinations could influence the infection with A.a., P.g., P.i., T.f. and T.d.. However, the mechanisms of the HLA - bacteria association are unknown. As well as bacterial mimicry with HLA (Ebringer 1983) and HLA dependent immunoreactivity to bacterial antigens (Buckley et al. 1973, Greenberg et al. 1975) could be assumed. In addition another study revealed that HLA-B8:DR3 positive subjects showed the significant lowest levels of serum IgA (Modica et al. 1989). This finding could be related to the high incidence of an A.a. infection among HLA-B*08:Cw*07:DRB1*03:DRB3*:DQB1*02 positive patients. Further studies about the binding of periodontopathic and protective peptides at striking HLA molecules are required.

Literature

  • Buckley CE, Dorsey FC, Corley RB, Ralph WB, Woodbury MA, Amos DB: HL-A linked immune-response genes. Proceedings of the National Academy of Sciences of the United States of America 1973, 70, S. 2157-2161.
  • Ebringer A: Ankylosing spondylarthritis, HLA B27 and the theory of crossed tolerance. Revue du rhumatisme et des maladies osteo-articulaires 1983, 50, S. 763-769.
  • Greenberg LJ, Gray ED, Yunis EJ: Association of HL-A 5 and immune responsiveness in vitro to streptococcal antigens. The Journal of experimental medicine 1975, 141, S. 935-943.
  • Hjelmstrom P, Giscombe R, Lefvert AK, Pirskanen R, Kockum I, Landin-Olsson M, Sanjeevi CB:Polymorphic amino acid domains of the HLA-DQ molecule are associated with disease heterogeneity in myasthenia gravis.Journal of Neuroimmunology 1996, 65, S. 125-131.
  • Machulla HK, Schonermarck U, Schaaf A, Muller LP, Kloss C, Kruger J, Kunze G, Schonermarck G, Langner J: HLA-A, B, Cw and DRB1, DRB3/4/5, DQB1, DPB1 frequencies in German immunoglobulin A-deficient individuals. Scandinavian journal of immunology 2000, 52, S. 207-211.
  • Modica MA, Freddi S, Caruso C: Blood IgA, IgM and IgE levels are influenced by sex and HLA phenotype. Experimental and clinical immunogenetics 1989, 6, S. 251-257.
  • Nunes IP, Johannessen AC, Matre R, Kristoffersen T: Epithelial expression of HLA class II antigens and Fc gamma receptors in patients with adult periodontitis. Journal of Clinical Periodontology 1994, 21, S. 526-532.
  • Reichert S, Stein J, Gautsch A, Schaller HG, Machulla HK: Gender differences in HLA phenotype frequencies found in German patients with generalized aggressive periodontitis and chronic periodontitis. Oral microbiology and immunology. 2002, 17, S. 360-368.
  • Stein J, Reichert S, Gautsch A, Machulla HK: Are there HLA combinations typical supporting for or making resistant against aggressive and/or chronic periodontitis? Journal of Periodontal Research 2003, 38, S. 508-517.

Abbreviations

HLA human leucozyte antigen
AP aggressive periodontitis
CP chronic periodontitis
PCR-SSP polymerase chain reaction with sequence-specific primers
A.a. Actinobacillus actinomycetemcomotans
P.g. Porphyromonas gingivalis
P.i. Prevotella intermedia
T.f. Tannerella forsytensis
T.d. Treponema denticola

This Poster was submitted by OA Dr. Stefan Reichert.

Correspondence address:
OA Dr. Stefan Reichert
Universitätspoliklinik für Zahnerhaltungskunde und Parodontologie
Martin-LutherUniversität Halle-Wittenberg
Große Steinstrasse 19
06108 Halle (Saale)