Background/Purpose:

Periodontitis (PD) has been implicated in rheumatoid arthritis (RA) pathogenesis including the expression of anti-citrullinated protein antibody (ACPA).  ACPA, in turn, have been shown to be robust predictors of radiographic progression in RA with recent evidence suggesting that ACPA targeting citrullinated vimentin could directly mediate disease-related bone damage.  We sought to examine the relationship of alveolar bone loss (a feature of PD) with RA disease activity and autoantibody expression, including ACPA.

Methods:

Panoramic radiographs were collected in RA patients and scored by two investigators (ICC 0.85) blinded to PD status.  Patients were categorized into low, moderate, or high tertiles based on the mean bone loss across sites (up to 24 sites were examined per patient).  PD was defined using a standardized periodontal exam and the criteria of Machtei et al (J Periodontol, 1990).  ACPA concentrations were measured via 2^ndgeneration ELISA (aCCP2) and by a bead-based multiplex antigen array on the BioPlex Platform , the latter to assess distinct antigen-specific ACPA.  Associations of moderate and high bone loss (vs. low) with disease characteristics were examined using multivariable (MV) regression (covariates: age, gender, race, BMI, smoking, HLA-DRB1 SE, PD prednisone use, sicca symptoms, and others) identified through stepwise selection.  Antigen-specific ACPA responses were compared across tertiles in aCCP2 positive patients using Significance Analysis of Microarrays (SAM) with separate analyses in ever and never smokers. 

Results:

 RA patients (n = 274) were primarily male (63%), Caucasian (78%), ever smokers (62%), and had a mean age of 59 (±12) years.  Approximately 1 in 3 patients (35%) had PD.  Of those with PD, most had high (66%) and moderate (24%) levels of bone loss with fewer showing low bone loss (10%).  Disease characteristics based on alveolar bone loss are shown (Table).  Following MV adjustment, increased alveolar bone loss remained significantly associated with higher values of aCCP2, DAS-28-CRP, HAQ, tender joint counts, and joint space narrowing scores.  Microarray analyses limited to aCCP2 positive patients demonstrated that ACPA targeting citrullinated vimentin and histone were significantly increased (q-value < 0.1%) in the moderate and high bone loss groups vs. low group, irrespective of smoking status. 

Conclusion:

Alveolar bone loss, a well-recognized feature of chronic PD, is strongly associated with increased RA disease activity.   Furthermore, these results suggest that ACPA targeting, potentially of both vimentin and histones could represent potentially important links between RA and alveolar bone loss, providing novel insight into the disproportionate frequency of periodontal bone damage that has been reported in RA.

Table:  RA-related measures of disease activity & severity based on low, moderate, or high tertile of alveolar bone loss (unadjusted p-values shown)

 

	Low (n=88)	Moderate (n=85)	High (n=101)	P-Value
Tender joint count (0-28)	2.6 (4.8)	3.0 (4.2)	4.0 (4.9)	0.002
Swollen joint count (0-28)	3.0 (3.5)	3.4 (4.7)	4.2 (4.3)	0.041
DAS-28-CRP	2.4 (1.2)	2.6 (1.1)	3.0 (1.1)	< 0.001
HAQ disability (0-3)	0.6 (0.7)	0.8 (0.7)	1.0 (0.7)	0.001
Pain (0-10)	2.7 (2.5)	3.0 (2.4)	3.9 (2.7)	0.007
Anti-CCP2, U/ml	145 (122)	162 (117)	203 (119)	0.007
RF, IU/ml	200 (519)	273 (465)	281 (490)	0.002
Total Sharp Score	13.2 (16.4)	18.1 (20.4)	25.8 (25.4)	0.003
Erosion Score	2.7 (4.7)	4.4 (7.8)	5.7 (8.7)	0.041
JSN Score	10.5 (13.3)	13.8 (14.5)	20.1 (19.3)	< 0.001

 

 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/alveolar-bone-loss-is-associated-with-disease-activity-and-acpa-expression-in-rheumatoid-arthritis/