Autoantibodies against citrullinated histone H3 in rheumatoid arthritis and periodontitis patients

Janssen, Koen M. J.; Smit, Menke J. de; Withaar, Coenraad; Brouwer, Elisabeth; Winkelhoff, A.J. van; Vissink, Arjan; Westra, Johanna

doi:10.1111/jcpe.12727

Cited by 37 publications

(31 citation statements)

References 29 publications

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“…4b and d ). These findings are fully consistent with the previously published observation that citrullinated histone H3 is abundantly detectable in inflamed periodontal tissue ( 28 ). Thus, P. gingivalis is capable of neutralizing a major NET-associated histone implicated in bacterial elimination in the periodontium, where PPAD is clearly detectable ( Fig.…”

Section: Resultssupporting

confidence: 93%

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A Secreted Bacterial Peptidylarginine Deiminase Can Neutralize Human Innate Immune Defenses

Stobernack

Espina

Mulder

et al. 2018

mBio

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Bacterial pathogens do not only succeed in breaking the barriers that protect humans from infection, but they also manage to evade insults from the human immune system. The importance of the present study resides in the fact that protein citrullination is shown to represent a new bacterial mechanism for immune evasion. In particular, the oral pathogen P. gingivalis employs this mechanism to defuse innate immune responses by secreting a protein-citrullinating enzyme. Of note, this finding impacts not only the global health problem of periodontitis, but it also extends to the prevalent autoimmune disease rheumatoid arthritis, which has been strongly associated with periodontitis, PPAD activity, and loss of tolerance against citrullinated proteins, such as the histone H3.

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Section: Resultssupporting

confidence: 93%

“…Immunohistochemical staining of PPAD was performed as described before ( 28 ). Briefly, human paraffin-embedded gingival tissues were collected from P. gingivalis -colonized periodontitis patients at the dentistry department of the University Medical Center Groningen.…”

Section: Methodsmentioning

confidence: 99%

A Secreted Bacterial Peptidylarginine Deiminase Can Neutralize Human Innate Immune Defenses

Stobernack

Espina

Mulder

et al. 2018

mBio

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“…More recently, the presence of anticitrullinated histone H3 autoantibodies was investigated: these biomarkers were found in 39% of RA patients compared to 8% in HC and 10% in PD patients. No associations were found between anticitrullinated histone H3 levels and periodontal status in RA patients [52].…”

Section: Autoantibodiesmentioning

confidence: 99%

Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators?

Ceccarelli

Saccucci

Carlo

et al. 2019

Mediators of Inflammation

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The strict link between periodontitis (PD) and rheumatoid arthritis (RA) has been widely demonstrated by several studies. PD is significantly more frequent in RA patients in comparison with healthy subjects: this prevalence is higher in individuals at the earliest stages of disease and in seropositive patients. This is probably related to the role of P. gingivalis in inducing citrullination and leading to the development of the new antigens. Despite the many studies conducted on this topic, there is very little data available concerning the possibility to use the same biomarkers to evaluate both RA and PD patients. The aim of the review is to summarize this issue. Starting from genetic factors, data from literature demonstrated the association between HLA-DRB1 alleles and PD susceptibility, similar to RA patients; moreover, SE-positive patients showed simultaneously structural damage to the wrist and periodontal sites. Contrasting results are available concerning other genetic polymorphisms. Moreover, the possible role of proinflammatory cytokines, such as TNF and IL6 and autoantibodies, specifically anticyclic citrullinated peptide antibodies, has been examined, suggesting the need to perform further studies to better define this issue.

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“…The systemic effects of NETs in periodontal disease may contribute to the body’s overall inflammatory burden, worsening conditions such as diabetes mellitus, obstructive pulmonary disease, and atherosclerosis ( 56 – 60 ). Further, periodontitis-derived citrullinated histones ( 8 , 61 ) may trigger autoimmunity, especially in rheumatoid arthritis.…”

Section: Mini-reviewmentioning

confidence: 99%

Janus-Faced Neutrophil Extracellular Traps in Periodontitis

et al. 2017

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Periodontitis is characterized by PMN infiltration and formation of neutrophil extracellular traps (NETs). However, their functional role for periodontal health remains complex and partially understood. The main function of NETs appears to be evacuation of dental plaque pathogen-associated molecular patterns. The inability to produce NETs is concomitant with aggressive periodontitis. But in cases with exaggerated NET production, NETs are unable to maintain periodontal health and bystander damages occur. This pathology can be also demonstrated in animal models using lipopolysaccharide as PMN activator. The progress of periodontitis appears to be a consequence of the formation of gingival pockets obstructing the evacuation of both pathogen-associated and damage-associated molecular patterns, which are responsible for the self-perpetuation of inflammation. Thus, besides the pathogenic effects of the periodontal bacteria, the dysregulation of PMN activation appears to play a main role in the periodontal pathology. Consequently, modulation of PMN activation might be a useful approach to periodontal therapy.

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Autoantibodies against citrullinated histone H3 in rheumatoid arthritis and periodontitis patients

Cited by 37 publications

References 29 publications

A Secreted Bacterial Peptidylarginine Deiminase Can Neutralize Human Innate Immune Defenses

A Secreted Bacterial Peptidylarginine Deiminase Can Neutralize Human Innate Immune Defenses

Periodontitis and Rheumatoid Arthritis: The Same Inflammatory Mediators?

Janus-Faced Neutrophil Extracellular Traps in Periodontitis

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