Session Information
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: RA-related autoantibodies are typically elevated prior to the onset of RA. Screening for autoantibody (aAb) positive individuals is a means to assemble a cohort at very high risk for future RA for epidemiologic and intervention studies. However, little is known about the stability of RA-related aAbs over time in individuals without RA who screen positive in a non-clinical setting.
Methods: Studies of the Etiology of RA (SERA) prospectively follows subjects who are RA-free but are at increased risk for future RA because they are a first-degree relative (FDR) of an RA proband (n=1774), or are from a cohort enriched for HLA-DR4 alleles (n=631). We tested serum aAbs to CCP (CCP2 and/or CCP3.1), RF, and RF IgG, IgA and IgM isotypes. Positivity was based on cut-offs as defined by manufacturer’s recommendations (CCP and RF isotypes) or ACR recommendations (RF). Overall, 23% (551/2405) tested positive for at least one aAb during screening. To evaluate outcomes of aAb+ subjects identified via screening, the cohort was limited to those who had at least one follow-up visit after their 1staAb+ visit (n= 315). For prediction analyses, we explored high titer aAb, as defined by 2-times (2x) and 3-times (3x) the cutoff.
Results: Over a mean follow-up of 5.1 years, 146 (46.3%) remained aAb+ at all visits (Persistent), 61 (19.4%) were aAb+ again on at least one follow-up visit, but fluctuated between aAb negative and aAb+ during follow-up (Intermittently Positive), and 108 (34.3%) were seronegative on all follow-up visits (Reverter) (Table 1). To address the question as to what predicts a person will test aAb+ again in those who were screened-positive, we combined the Persistent and Intermittently Positive groups to form a group that was aAb+ on two or more occasions (n=207). To examine the likelihood of testing aAb+ again after a screened-positive test, we conducted bivariate logistic regression models with every variable listed in Table 1 as a potential predictor. Table 2 lists the variables significantly associated with testing positive again. Age, sex, race/ethnicity, FDR status, shared epitope status, ever smoking, high CRP, and joint signs were not associated with testing aAb+ after the initial screened aAb+ test.
Conclusion: In this cohort of at-risk individuals who screen aAb+, the presence of any aAb at > 2x cutoff at screening predicts who will test positive again, while a 3x cutoff does not improve prediction. Demographic and environmental exposures were not associated aAb+ persistence, perhaps due to their primary influence at other stages of disease, including the initial development of RA-related aAbs.
| Table 1. Characteristics of Individuals in SERA who Tested Positive for an RA-related Autoantibody During Screening stratified by Autoantibody Status on Follow-up | |||
|
|
Persistent N = 146 |
Intermittently Positive N = 61 |
Reverter N = 108 |
| Age at first positive visit (Mean±SD) |
47.6±16.5 |
46.4±17.0 |
45.2±14.6 |
| Number of visits (including screening) (Mean±SD) |
3.4±1.7 |
4.7±1.5 |
2.9±1.3 |
| Length of Follow-up in years (Mean±SD) |
3.9 ±2.6 |
5.8±2.5 |
4.0±2.7 |
| Sex (%female) |
111 (76.0) |
50 (82.0) |
78 (72.2) |
| Race/Ethnicity (%Non-Hispanic White) |
116 (79.5) |
53 (86.9) |
78 (72.2) |
| First Degree Relative of an RA Proband (%) |
119 (81.5) |
55 (90.2) |
87 (80.6) |
| Shared Epitope positive (%) |
70 (48.0) |
39 (63.9) |
64 (59.3) |
| Ever smoker (%) |
51 (34.9) |
23 (37.7) |
42 (38.9) |
| CRP+ at first positive visit (%) |
47 (32.2) |
19 (31.2) |
30 (27.8) |
| CCP+ at first positive visit† (%) |
54 (37.0) |
12 (19.7) |
17 (15.7) |
| CCP+ > 2x cutoff at first positive visit† (%) |
40 (27.4) |
4 (6.6) |
6 (5.6) |
| CCP+ >3x cutoff at first positive visit† (%) |
32 (21.9) |
2 (3.3) |
6 (5.6) |
| RF+ at first positive visit (%) |
53 (36.3) |
18 (29.5) |
27 (25.0) |
| RF+ > 2x cutoff at first positive visit (%) |
25 (17.1) |
4 (6.6) |
4 (3.7) |
| RF+ > 3x cutoff at first positive visit (%) |
14 (9.6) |
2 (3.3) |
3 (2.8) |
| RF isotype+ at first positive visit‡ (%) |
98 (67.1) |
43 (70.5) |
73 (67.6) |
| RF isotype+ > 2x cutoff at first positive visit‡ (%) |
51 (34.9) |
13 (21.3) |
11 (10.2) |
| RF isoty pe+ > 3x cutoff at first positive visit‡ (%) |
41 (28.1) |
6 (9.8) |
5 (4.6) |
| ≥1 Swollen joint at first positive visit* (%) |
13/121 (10.7) |
8/51 (15.7) |
10/90 (11.1) |
| ≥1 Tender or swollen joint at first positive visit* (%) |
34/121 (28.1) |
11/51 (21.6) |
26/90 (28.9) |
| †Either CCP2 or CCP3.1 ‡ IgM, IgG, or IgA *joints included are: wrist, MCP, PIP, MTP and elbow; 57 individuals excluded due to missing exam data. | |||
| Table 2. Factors associated with the likelihood of testing autoantibody positive after the first positive (screening) test | |||
|
aAb status at first positive (screening) visit |
OR (95% CI)* |
p-value |
Percentage who test aAb positive again |
| Any aAb+ (definition of cohort) |
– |
– |
65.7% |
| Any aAb+ > 2x cutoff |
5.50 (3.15-9.61) |
<0.01 |
85.2% |
| Any aAb+ > 3x cutoff |
4.49 (2.40-8.41) |
<0.01 |
85.6% |
| CCP+ † |
2.51 (1.38-4.54) |
<0.01 |
79.5% |
| CCP+ > 2x cutoff † |
4.59 (1.89-11.15) |
<0.01 |
88.0% |
| CCP+ > 3x cutoff † |
3.34 (1.36-8.23) |
<0.01 |
85.0% |
| RF+ |
1.57 (0.93-2.64) |
0.09 |
72.4% |
| RF+ > 2x cutoff |
4.23 (1.45-12.38) |
<0.01 |
87.9% |
| RF+ > 3x cutoff |
4.23 (1.45-12.38) |
0.08 |
84.2% |
| RF+ isotype ‡ |
1.02 (0.62-1.69) |
0.92 |
65.9% |
| RF+ isotype >2x cutoff ‡ |
3.95 (1.98-7.87) |
<0.01 |
85.3% |
| RF+ isotype >3x cutoff ‡ |
6.05 (2.33-15.72) |
<0.01 |
90.4% |
| *OR represents the increased odds of testing positive again given their particular aAB+ status (and titer) at the first positive visit. †Either CCP2 or CCP3.1 ‡IgM, IgG, or IgA | |||
To cite this abstract in AMA style:
Norris JM, Bemis EA, Demoruelle MK, Weisman M, Buckner JH, Gregersen PK, Mikuls TR, O'Dell JR, Keating RM, Deane KD, Holers VM. Factors Predicting Likelihood of Remaining Positive for Rheumatoid Arthritis-Related Autoantibodies Following Autoantibody Screening [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/factors-predicting-likelihood-of-remaining-positive-for-rheumatoid-arthritis-related-autoantibodies-following-autoantibody-screening/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/factors-predicting-likelihood-of-remaining-positive-for-rheumatoid-arthritis-related-autoantibodies-following-autoantibody-screening/