Is there a link between carbamylation and citrullination in periodontal disease and rheumatoid arthritis?

Bright, Richard; Proudman, Susanna; Rosenstein, Elliot D.; Bartold, P. Mark

doi:10.1016/j.mehy.2015.03.006

Cited by 35 publications

(37 citation statements)

References 63 publications

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“…14,18 In addition, one preliminary report has demonstrated the presence of carbamylated proteins in inflamed human gingiva. 19 These findings correlate well with a report demonstrating that induction of autoimmunity to citrullinated proteins can be associated with citrullination of proteins within inflamed periodontal tissues. 20 In particular these proteins appear to be closely associated with the inflammatory cell infiltrate within the gingival connective tissues of mild and moderate periodontitis samples.…”

Section: Discussionsupporting

confidence: 91%

Gingival tissue, an extrasynovial source of malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins

Bright

Thiele

Manavis

et al. 2017

J of Periodontal Research

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Background and Objective Postranslational modification of proteins can lead to the production of autoantibodies and loss of immune tolerance. This process has been hypothesised to be a critical factor in the pathogenesis of rheumatoid arthritis. The objective of this study was to demonstrate that inflamed human gingival tissue provides an extrasynovial source of malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins all of which are considered to be linked to the development of rheumatoid arthritis. Identification of such modified proteins in inflamed gingiva may explain, in part, how inflammation of the periodontal tissues may influence the development of rheumatoid arthritis. Material and Methods Gingival biopsies of healthy, mild and moderate periodontitis were triple stained with antibodies against malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins. Results Assessment of healthy gingival tissue revealed negligible staining for carbamylated, malondialdehyde‐acetaldehyde (MAA), or citrullinated proteins. Mild periodontitis was positive for all three modifications. Furthermore, there was an increase in staining intensity for carbamylated, citrullinated and MAA‐modified proteins in moderate periodontitis. Negative staining results were observed for the isotype controls. Conclusion This study provides evidence for the presence of citrullinated, carbamylated and MAA adduct modified proteins in inflamed periodontal tissues. The potential for these proteins to play a role in autoimmunity in a multi‐system inflammatory syndromic disease model now needs to be determined.

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Section: Discussionsupporting

confidence: 91%

Gingival tissue, an extrasynovial source of malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins

Bright

Thiele

Manavis

et al. 2017

J of Periodontal Research

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“…Citrullination is a common posttranslational modification of proteins based on the enzymatic conversion of peptidylarginine into peptidyl‐citrulline 40 . Extra‐articular citrullination and the production of ACPAs have been documented as priming immunologic events in many tissues, including in inflamed gingival tissues associated with periodontal disease 6 , 41 . These findings seem to support the hypothesis that the presence of P. gingivalis infection, as assessed by antibody titer, is an early marker of RA risk.…”

Section: Discussionmentioning

confidence: 70%

Periodontal Disease in Individuals With a Genetic Risk of Developing Arthritis and Early Rheumatoid Arthritis: A Cross‐Sectional Study

Bello-Gualtero

Lafaurie

Hoyos

et al. 2016

Journal of Periodontology

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“…Anti-cyclic citrullinated peptide (anti-CCP) antibodies and citrullinated peptides (a-enolase, vimentin, fibrinogen, and Type II collagen) are associated with breakdown of self-tolerance in RA. [23] RA is genetically associated with HLA DR-4 locus containing shared epitopes, i.e., 0401, 0404, 0405, 0408 which is also associated with severe and aggressive periodontitis. Cells, enzymes, and cytokines are also common in both the diseases.…”

Section: Immunopathogenesis Of Chronic Periodontitismentioning

confidence: 99%

“…[33] Extra articular citrullination occurs in lungs of smokers. [23] During citrullination, arginine is converted into citrulline that results in change in mass of citrulline by 0.984 Da and loss of one positive charge which also has effect on isoelectric point (pI). The pI value of arginine and citrulline is 11.41 and 5.91, respectively.…”

Section: Immunopathogenesis Of Chronic Periodontitismentioning

confidence: 99%

Relationship between rheumatoid arthritis and chronic periodontitis

Batool¹,

Afzal²,

Shahzad³

et al. 2016

JMRPS

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Chronic periodontitis is inflammation of supporting structures of teeth caused by microorganisms, and Porphyromonas gingivalis is one of the most common organisms. Periodontitis has been associated with different systemic diseases and rheumatoid arthritis (RA) is one of them. Periodontitis and RA share several features such as inflammation and bone destruction. Enzyme peptidyl arginine deaminase (PAD) is responsible for citrullination of arginine and citrullinated antigens are generated by posttranslational modification. Anti-cyclic citrullinated peptide antibodies and citrullinated peptides (a-enolase, vimentin, fibrinogen, and Type II collagen) are associated with breakdown of self-tolerance in RA. P. gingivalis is the only periodontopathic organism to produce PAD that is responsible for citrullination of arginine. Therefore, patients of periodontitis should be evaluated for RA.

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Is there a link between carbamylation and citrullination in periodontal disease and rheumatoid arthritis?

Cited by 35 publications

References 63 publications

Gingival tissue, an extrasynovial source of malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins

Gingival tissue, an extrasynovial source of malondialdehyde‐acetaldehyde adducts, citrullinated and carbamylated proteins

Periodontal Disease in Individuals With a Genetic Risk of Developing Arthritis and Early Rheumatoid Arthritis: A Cross‐Sectional Study

Relationship between rheumatoid arthritis and chronic periodontitis

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