Session Information
Date: Sunday, November 5, 2017
Title: Rheumatoid Arthritis – Human Etiology and Pathogenesis Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Anti-citrullinated protein antibody (ACPA) reactivities can precede RA onset, and may be involved in the pathogenesis of the disease. We wanted to assess the prevalence of baseline ACPA reactivities in an inception cohort of early RA patients, including subgroups based on anti-CCP/RF status, and to compare the findings to healthy controls.
Methods: 217 DMARD-naïve early RA patients from the ARCTIC trial (1) were analyzed. Radiographs were scored according to van der Heijde Sharp (vdHS) score. Anti-CCP status was analyzed by FEIA (positive if ≥10 IU/mL) and RF by ELISA (positive if ≥25 IU/mL). ACPA titres (AU/ml) were considered positive if above the 98-percentile of values in 619 non-RA subjects. Analysis of 13 ACPA reactivities targeting citrullinated peptides from fibrinogen, alpha-1 enolase, vimentin, fillagrin and histone was performed at baseline in patients and 94 controls (blood donors matched for age/gender/smoking), using a multiplex chip-based assay (2). Positivity and median number of ACPA reactivities in the subgroups were compared using Chi-square test and Mann-Whitney U-test, respectively.
Results: Baseline characteristics are presented in the table. The median [IQR] number of antibody reactivities in all patients was 7[3,10], compared to 0[0,0] in controls (p<0.001, figure). The corresponding numbers were 8[5,10] and 0[0,1] for the anti-CCP+ vs. anti-CCP- patients (p<0.0001), 8[5,10] and 2[0,8] for the RF+ vs. RF- patients (p<0.001), and 8[6,10] and 0[0,1] for the anti-CCP+/RF+ vs. the anti-CCP-/RF- (p<0.001) (table, figure). Positivity for ACPA reactivities was seen mainly in the anti-CCP+, RF+ and anti-CCP+/RF+ patients, but also occurred more frequently in the anti-CCP-, RF- and anti-CCP-/RF- patients than in controls (anti-CCP- vs controls p=0.002, RF- vs controls p<0.001, and anti-CCP-/RF- vs. controls p=0.035) (table).
Table: Baseline characteristics
|
Anti-CCP+ n=178 |
Anti-CCP- n=39 |
RF+ n=154 |
RF- n=63 |
Anti-CCP+/RF+ n=147 |
Anti- CCP-/RF- n=32 |
All RA n=217 |
Control n=94 |
Age, years1 |
50.8(13.2) |
55.0(14.9) |
51.9(13.3) |
50.8(14.2) |
51.7(13.6) |
55.0(16.1) |
51.5(13.6) |
52(9.4) |
Female2 |
109(61) |
22(56) |
91(59) |
40(63) |
86(59) |
17(53) |
131(60) |
63(59) |
Ever-smoker2 |
122(69) |
26(67) |
109(71) |
39(62) |
103(70) |
20(62) |
148(68) |
81(64) |
DAS1 |
3.4(1.1) |
4.0(1.3) |
3.5(1.2) |
3.5(1.2) |
3.42(1.13) |
3.9(1.2) |
3.5(1.2) |
NA |
vdHS score3 |
4[1.5,7.9] |
4.5[2,10] |
4.5[2,8] |
3.5[1.5,9.8] |
4.5[2,8] |
5.5[1.9,12.6] |
4 [1.5,8] |
NA |
Vim 60-75cit4 |
152(85) |
7(18) |
130(84) |
29(46) |
128(87) |
5(16) |
159(73) |
5(5) |
H4 31-50cit4 |
142(80) |
3(8) |
119(77) |
26(41) |
118(80) |
2(6) |
145(67) |
1(1) |
CEP14 |
137(77) |
3(8) |
117(76) |
23(37) |
115(78) |
1(3) |
140(65) |
1(1) |
Fil 307-324cit4 |
134(75) |
2(5) |
113(73) |
23(37) |
112(76) |
1(3) |
136(63) |
0(0) |
Fib 573cit4 |
121(68) |
2(5) |
99(64) |
24(38) |
99(67) |
2(6) |
123(57) |
0(0) |
Fib 36-52cit4 |
116(65) |
1(3) |
96(62) |
21(33) |
96(65) |
1(3) |
117(54) |
2(2) |
H3 1-30cit4 |
106(60) |
1(3) |
93(60) |
14(22) |
92(63) |
0(0) |
107(49) |
0(0) |
H4 14-34cit4 |
103(58) |
2(5) |
90(58) |
15(24) |
88(60) |
0(0) |
105(48) |
3(3) |
H3 21-44cit4 |
94(53) |
2(5) |
80(52) |
16(25) |
79(54) |
1(3) |
96(44) |
1(1) |
Vim 2-17cit4 |
87(49) |
1(3) |
80(52) |
8(13) |
79(54) |
0(0) |
88(41) |
0(0) |
Fib 591cit4 |
66(37) |
3(8) |
56(36) |
13(21) |
55(37) |
2(6) |
69(32) |
1(1) |
Fib 74cit4 |
60(34) |
6(15) |
54(35) |
12(19) |
51(35) |
3(9) |
66(30) |
3(3) |
Fib 72cit4 |
24(13) |
3(8) |
21(14) |
6(1) |
20(14) |
2(6) |
27(12) |
2(2) |
Number of ACPA reactivities3 |
8[5,10] |
0[0,1] |
8[5,10] |
2[0,8] |
8[6,10] |
0[0,1] |
7[3,10] |
0[0,0] |
1Mean(SD), 2n(%), 3median[IQR], 4n positive(%)
Figure: Number of ACPA reactivities per patient
Conclusion: Prevalence of ACPA reactivities differed in subgroups of DMARD-naïve early RA patients according to anti-CCP and RF status. In general, higher numbers of ACPA reactivities were seen in anti-CCP+ patients, but all RA subgroups, including anti-CCP-, RF- and anti-CCP-/RF- patients, had higher prevalence of ACPA reactivities compared to healthy controls.
References: 1) Haavardsholm et al BMJ 2016, 2) Hansson et al Arthr Res Ther 2012
To cite this abstract in AMA style:
Jonsson MK, Hensvold A, Hansson M, Mathsson-Alm L, Aga AB, Sexton J, Fevang BT, Lillegraven S, Catrina AI, Haavardsholm EA. Anti-Citrullinated Protein Antibody Reactivities in Treatment NaïVe Early Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/anti-citrullinated-protein-antibody-reactivities-in-treatment-naive-early-rheumatoid-arthritis/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-citrullinated-protein-antibody-reactivities-in-treatment-naive-early-rheumatoid-arthritis/