Session Information
Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Clinical characteristics and biomarkers help clinicians predict disease features in rheumatoid arthritis (RA). Both peptidylarginine deiminase 4 (PAD4) antibodies and smoking have been associated with common clinical characteristics in RA, namely erosive disease, anti-CCP positivity, and interstitial lung disease. Whether smoking is etiologically linked to developing PAD4 antibodies, however, is unknown. We evaluated whether smoking history was associated with PAD4 antibody development in RA.
Methods: Adults with physician-diagnosed RA were drawn from a longitudinal cohort followed at the Johns Hopkins Arthritis Center. PAD4 and PAD3/4 cross-reactive antibodies were measured by immunoprecipitation; anti-CCP levels were measured by ELISA. Genotyping for shared epitope (SE) alleles was performed. Clinical data were drawn from patient/physician reported and historical sources.
Results: Among the 274 patients with RA, demographics did not significantly differ in those with PAD4, PAD3/4 and without PAD4 antibodies (table 1). Disease duration was longer in PAD4 and PAD3/4 antibody positive groups compared with the PAD4 negative group, whereas presence of SE was higher in the PAD4 antibody group. Both PAD4 and PAD3/4 positive groups were more likely to be anti-CCP positive. There was no significant difference in smoking history between groups, but there was a trend toward lower frequency of current smokers among those with PAD4 antibodies. In subsequent analyses, all those with PAD4 antibodies were grouped (PAD4 only and PAD3/4). In stratified analyses (table 2), smoking history remained unassociated with PAD4 antibody status, and was inversely associated with having PAD4 antibodies in those with SE, although not statistically significant. In multivariable models adjusting for disease duration, SE, race and sex, smoking remained unassociated with PAD4 antibody presence, while longer disease duration and having SE were positively associated with PAD4 antibodies (table 3).
Conclusion: Smoking history was not associated with the development of PAD4 or PAD3/4 cross-reactive antibodies in this cohort with RA. The lack of association persisted in multivariable analyses accounting for potentially confounding features. Having shared epitope and longer disease duration, however, were associated with developing PAD4 antibodies.
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Table 1: Demographic and clinical features of PAD4 antibody positive, PAD 3/4 antibody positive and PAD4 antibody negative groups |
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|
Variable |
PAD negative (P0) (n= 206) |
PAD 4 Ab only (P4) (N= 34) |
PAD 3/4 Ab (XR) (N = 34) |
p-value XR vs P0 |
p-value P4 vs P0 |
p-value XR vs P4 |
|
Female sex- N (%) |
163 (79%) |
27 (79%) |
28 (82%) |
0.66 |
0.99 |
0.76 |
|
Race- N (%) |
White 165 (80%) Black 27 (13%) Asian/Other 14 (7%) |
White 28 (82.4%) Black 4 (11.8%) Asian/Other 2 (6%) |
White 27 (79%) Black 4 (12%) Asian/Other 3 (9%) |
0.91 |
0.99 |
0.95 |
|
Age- median (IQR) |
57 (49-66) |
55 (47-68) |
51.5 (46-64) |
0.14 |
0.70 |
0.33 |
|
Disease duration (yrs)- median (IQR) |
6 (2-12) |
15.5 (8-27) |
15.5 (7-26) |
<0.01 |
<0.01 |
0.77 |
|
Smoking status- N (%) |
Never 110 (54%) Former 71 (35%) Current 24 (12%) |
Never 18 (53%) Former 13 (38.2%) Current 3 (8.8%) |
Never 22 (65%) Former 12 (35%) Current 0 (0%) |
0.10 |
0.87 |
0.18 |
|
CCP positive- N (%) |
116 (57%) |
30 (88.2%) |
30 (88.2%) |
<0.01 |
<0.01 |
1.0 |
|
Shared Epitope- N (%) |
112 (54%) |
28 (82.4%) |
22 (64.7%) |
0.26 |
<0.01 |
0.10 |
|
Erosions- N (%) |
88 (43%) |
17 (54.8%) |
22 (65%) |
0.07 |
0.46 |
0.42 |
|
CDAI- median (IQR) |
7.9 (3-16) |
7 (2.8-11.5) |
3.7 (1.5-9.5) |
0.04 |
0.37 |
0.21 |
|
On a csDMARD- N (%) |
184 (90%) |
28 (82%) |
28 (82%) |
0.20 |
0.21 |
1.0 |
|
On methotrexate- N (%) |
127 (63%) |
20 (59%) |
24 (71%) |
0.33 |
0.73 |
0.31 |
|
On a biologic- N (%) |
89 (44%) |
17 (50%) |
16 (47%) |
0.71 |
0.49 |
0.81 |
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P0= PAD4 antibody negative; XR= PAD3/4 cross-reactive antibody; P4= PAD4 antibody only |
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Table 2: Stratified analyses of the association between smoking history and PAD4 antibody status |
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|
Odds ratio |
p-value |
|
|
With Shared Epitope |
0.67 |
0.25 |
|
Without Shared Epitope |
0.94 |
0.90 |
|
Females |
0.86 |
0.65 |
|
Males |
0.63 |
0.46 |
|
Disease duration > 10 years |
0.88 |
0.75 |
|
Disease duration < 10 years |
0.82 |
0.66 |
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Table 3: Unadjusted and adjusted associations between clinical variables and presence of PAD4 antibodies |
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|
Variable |
Odds Ratio (unadjusted) |
p-value |
Odds ratio (adjusted) |
p-value |
|
Female sex |
1.12 |
0.74 |
0.88 |
0.74 |
|
Non-white Race |
0.95 |
0.87 |
1.45 |
0.34 |
|
Ever Smoker |
0.81 |
0.46 |
0.78 |
0.41 |
|
Disease duration > 10 years |
3.64 |
< 0.01 |
3.46 |
<0.01 |
|
Presence of Shared epitope |
2.35 |
< 0.01 |
2.29 |
0.02 |
To cite this abstract in AMA style:
Cappelli L, Konig M, Naik P, Saleh A, Gelber AC, Bingham III CO, Darrah E. Disease Duration and Shared Epitope, but Not Smoking History, Are Associated with Peptidylarginine Deiminase 4-Antibody Development in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/disease-duration-and-shared-epitope-but-not-smoking-history-are-associated-with-peptidylarginine-deiminase-4-antibody-development-in-rheumatoid-arthritis/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/disease-duration-and-shared-epitope-but-not-smoking-history-are-associated-with-peptidylarginine-deiminase-4-antibody-development-in-rheumatoid-arthritis/