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Abstract Number: 812

Alveolar Bone Loss Is Associated With Disease Activity and ACPA Expression In Rheumatoid Arthritis

Ted R. Mikuls1, Jeffrey Payne2, Fang Yu3, Geoffrey M. Thiele4, Shawneen Gonzalez2, Jeffrey Markt5, Jeremy Sokolove6, William H. Robinson7, Richard J. Reynolds8, Grant W. Cannon9, David McGowan10, Gail S. Kerr11, Robert Redman12, Andreas M. Reimold13, Garth Griffiths14, Mark Beatty2, Marian Schmid2, Paul Johnson2, Debra Bergman15, Bartlett C. Hamilton III16, Alan R. Erickson1 and James R. O'Dell17, 1Omaha VA Medical Center and University of Nebraska Medical Center, Omaha, NE, 2College of Dentistry, University of Nebraska Medical Center, Lincoln, NE, 3University of Nebraska Medical Center, Omaha, NE, 4Int Med/Sec of Rheum/Immun, Univ of Nebraska Med Ctr, Omaha, NE, 5Otol-Head and Neck Surgery, University of Nebraska Medical Center, Omaha, NE, 6Stanford University, Palo Alto, CA, 7Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, 8Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 9Division of Rheumatology, Salt Lake City VA and University of Utah, Salt Lake City, UT, 10Dentistry, George E. Wahlen VA Medical Center, Salt Lake City, UT, 11Rheumatology, Washington DC VAMC, Georgetown and Howard University, Washington, DC, 12Dentistry, Washington DC VA, Georgetown and Howard University, Washington, DC, 13Rheumatology, Dallas VA and University of Texas Southwestern, Dallas, TX, 14Dentistry, Dallas VA and University of Texas Southwestern, Dallas, TX, 15Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 16University of Nebraska Medical Center and Omaha VA Medical Center, Omaha, NE, 17Dept of Internal Medicine, University of Nebraska Medical Center, Omaha, NE

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ACPA, Disease Activity, Periodontitis, radiography and rheumatoid arthritis (RA)

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Session Information

Session Title: Rheumatoid Arthritis - Autoantibodies and Citrullinated Proteins

Session Type: Abstract Submissions (ACR)

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 2ndgeneration 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

 

 


Disclosure:

T. R. Mikuls,

Roche/Genentech and Biogen IDEC Inc.,

2;

J. Payne,
None;

F. Yu,
None;

G. M. Thiele,
None;

S. Gonzalez,
None;

J. Markt,
None;

J. Sokolove,
None;

W. H. Robinson,
None;

R. J. Reynolds,
None;

G. W. Cannon,
None;

D. McGowan,
None;

G. S. Kerr,

Amgen, Abbott,

2;

R. Redman,
None;

A. M. Reimold,

UCB,

5,

Janssen Pharmaceutica Product, L.P.,

2,

Ardea,

2,

Novartis,

2,

Lilly,

2,

Pfizer,

2;

G. Griffiths,
None;

M. Beatty,
None;

M. Schmid,
None;

P. Johnson,
None;

D. Bergman,
None;

B. C. Hamilton III,
None;

A. R. Erickson,
None;

J. R. O’Dell,
None.

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