# Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study

**Authors:** Stefan Reichert, Wolfgang Schlumberger, Cornelia Dähnrich, Nora Hornig, Wolfgang Altermann, Hans-Günter Schaller, Susanne Schulz

PMC · DOI: 10.1186/s12967-015-0625-7 · Journal of Translational Medicine · 2015-08-29

## TL;DR

This study investigates if periodontal disease increases the risk of rheumatoid arthritis by looking at autoantibodies in patients with different types of gum disease.

## Contribution

The study provides new insights into the potential link between periodontitis and rheumatoid arthritis through autoantibody analysis.

## Key findings

- No significant association was found between periodontitis and anti-CCP or anti-CEP-1 autoantibodies.
- Presence of P. gingivalis was slightly linked to anti-CEP-1 positivity, but not significantly.
- HLA carriers showed a slight trend toward higher anti-CEP-1 positivity, but results were not statistically significant.

## Abstract

Periodontal disease could be a risk factor for rheumatoid arthritis (RA). It is assumed that the bacterial strain Porphyromonas gingivalis mediates citrullination of host peptides and thereby the generation of RA-associated autoantibodies in genetically predisposed individuals. For that reason non-RA individuals who suffered from generalized aggressive (GAgP, N = 51) and generalized chronic periodontitis (GChP, N = 50) were investigated regarding the occurrence of antibodies against citrullinated cyclic peptides (anti-CCP) and citrullinated α-enolase peptide-1 (anti-CEP-1) in comparison to non-RA non-periodontitis controls (N = 89). Furthermore, putative associations between infections with five periodontopathic bacteria or expression of certain human leucocyte antigens (HLA) to these autoantibodies were investigated.

The presence of anti-CCP and anti-CEP-1 in plasma samples was conducted with enzyme linked immunosorbent assay. Subgingival plaque specimens were taken from the deepest pocket of each quadrant and pooled. For detection of DNA of five periodontopathic bacteria PCR with sequence specific oligonucleotides was carried out. Low resolution HLA typing was carried out with PCR with sequence specific primers. Differences between patients and controls were assessed using Chi square test with Yates correction or Fisher`s exact test if the expected number n in one group was <5.

Two patients with GAgP (3.9 %), no patient with GChP and two controls (2.2 %, pFisher = 0.662) were positive for anti-CEP-1 whereas no study participant was anti-CCP positive. Individuals with P. gingivalis were slightly more often anti-CEP-1 positive in comparison to individuals without P. gingivalis (3.2 vs. 1.1 %, pFisher = 0.366). Carrier of HLA-DQB1*06 or the HLA combination DRB1*13; DRB3*; DQB1*06 were slightly more anti-CEP-1 positive (6.1 and 4.3 %) than no carriers (0.7 and 0 %, pFisher 0.053).

GAgP and GChP and the presence of periodontopathic bacteria are not associated with an increased risk for occurrence of anti-CCP and anti-CEP-1 autoantibodies. The putative relationship between periodontitis and RA should be investigated in further studies.

## Linked entities

- **Proteins:** HLA-DRB3 (major histocompatibility complex, class II, DR beta 3)
- **Diseases:** rheumatoid arthritis (MONDO:0008383)
- **Species:** Porphyromonas gingivalis (taxon 837)

## Full-text entities

- **Genes:** PRTN3 (proteinase 3) [NCBI Gene 5657] {aka ACPA, AGP7, C-ANCA, CANCA, MBN, MBT}, ENO1 (enolase 1) [NCBI Gene 2023] {aka ENO1-IT1, ENO1L1, HEL-S-17, MPB1, NNE, PPH}, HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) [NCBI Gene 3123] {aka DRB1, HLA-DR1B, HLA-DRB, SS1}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, VIM (vimentin) [NCBI Gene 7431], CNTRL (centriolin) [NCBI Gene 11064] {aka CEP1, CEP110, FAN, bA165P4.1}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, CHM (CHM Rab escort protein) [NCBI Gene 1121] {aka DXS540, GGTA, HSD-32, REP-1, TCD}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, PADI2 (peptidyl arginine deiminase 2) [NCBI Gene 11240] {aka PAD-H19, PAD2, PDI2}, HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) [NCBI Gene 3119] {aka CELIAC1, HLA-DQB, IDDM1}, PADI4 (peptidyl arginine deiminase 4) [NCBI Gene 23569] {aka PAD, PAD4, PADI5, PDI4, PDI5}
- **Diseases:** periodontal bacteria (MESH:C000719206), aggressive (MESH:D010554), endodontic lesions (MESH:D011671), inflammation (MESH:D007249), cartilage bone destruction (MESH:D002357), ChP (MESH:D055113), epileptics (MESH:D004827), gingival overgrowth (MESH:D019214), autoimmune (MESH:D001327), RA (MESH:D001172), diabetes mellitus (MESH:D003920), abscess formation (MESH:D058426), Angular bony defects (MESH:D065170), gingivitis (MESH:D005891), Morbus Crohn (MESH:D003424), osteoarthritis (MESH:D010003), AgP (MESH:D010520), Periodontitis (MESH:D010518), coronary heart disease (MESH:D003327), dental loss (MESH:D009057), bony defects (MESH:D018213), Bleeding (MESH:D006470), arthritis (MESH:D001168), calculus (MESH:D002137), infected (MESH:D007239), tooth loosening (MESH:D011475), gingival recession (MESH:D005889), bone loss (MESH:D001847), AL (MESH:D017622), Periodontal disease (MESH:D010510), rheumatic diseases (MESH:D012216)
- **Species:** Prevotella intermedia (species) [taxon 28131], Homo sapiens (human, species) [taxon 9606], Aggregatibacter actinomycetemcomitans (species) [taxon 714], Treponema denticola (species) [taxon 158], Tannerella forsythia (species) [taxon 28112], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Porphyromonas gingivalis (species) [taxon 837]

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## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC4552989/full.md

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Source: https://tomesphere.com/paper/PMC4552989