Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Citrullination and Peptidylarginine Deiminase (PAD) Expression Is Detected in the Oral Mucosa and Periodontium in the Absence of Rheumatoid Arthritis.

Bingham1,  Clifton O., Reynolds3,  Mark A., Giles2,  Jon, Andrade2,  Felipe, Bathon2,  Joan M., Fox-Talbot2,  Karen, Halushka2,  Marc K.

Johns Hopkins, Baltimore, MD
Johns Hopkins
University of Maryland Dental School


There is growing interest in the association of periodontal disease (PD) and rheumatoid arthritis (RA). It has been proposed that P. gingivalis, an important periodontal bacteria with an endogenous PAD enzyme (Pg-PAD), is responsible for oral citrullination leading to a break in tolerance with attendant anti- citrullinated peptide antibody (ACPA) formation in RA. There is limited data on the protein citrullination and endogenous PAD expression in the oral cavity.


Using immunohistochemistry, we have examined formalin-fixed, paraffin-embedded gingival tissue from 4 patients with PD. Additional oral tissues examined included buccal mucosa and tonsil. All samples were from patients without known inflammatory arthritis. We used an anti-modified citrulline kit (Upstate) to detect citrullination. Expression of PAD2, PAD3, PAD4, and PAD6 were evaluated with rabbit-anti human polyclonal antibodies using an avidin-biotin complex detection system with DAB as the chromogen and with appropriate controls.


Citrullination was detected in keratinized epithelium in gingiva and in normal buccal mucosa. Variable levels of citrullination were also detected in blood vessels and inflammatory cells in normal mucosa and periodontitis. Expression of PAD2 was abundant in buccal mucosa and periodontal tissues in epithelium, vascular endothelium, and inflammatory cells. PAD3 was similarly localized in the epithelium, endothelium, and inflammatory cells. PAD4 was only minimally expressed in the epithelium and weakly in the endothelium, but seen in some infiltrating cells including neutrophils and in inflammatory cells in tonsil. PAD6 was seen in the epithelium and endothelium with variable expression in inflammatory cells. In some tissue with skeletal muscle, bundles were variably stained with PAD2 and PAD6 with concomitant citrullination. Studies to examine PAD1 expression and additional diseased and control tissues are in progress.


This is the first comprehensive examination of protein citrullination and PAD expression in oral tissues. Citrullination is ubiquitously present in multiple oral locations and is not limited to inflamed periodontium. Similarly, PADs 2, 3, 4 and 6 are all localized in oral tissue in the presence or absence of inflammation. Our studies indicate that there are multiple potential pathways responsible for post-translational citrullination in the oral mucosa: endogenous PAD expression, upregulated PADs at inflammatory foci, in addition to Pg-PAD providing an exogenous source. Additional studies are necessary to determine the specific substrates of different human and bacterial PADs in the periodontal microenvironment and to establish their relationship with ACPA formation, and disease initiation or propagation in RA.

To cite this abstract, please use the following information:
Bingham, Clifton O., Reynolds, Mark A., Giles, Jon, Andrade, Felipe, Bathon, Joan M., Fox-Talbot, Karen, et al; Citrullination and Peptidylarginine Deiminase (PAD) Expression Is Detected in the Oral Mucosa and Periodontium in the Absence of Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1074
DOI: 10.1002/art.28841

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