Background
Methods
Design and setting of the study
Patients and controls
Laboratory examinations
Clinical and imaging assessments
Statistical analysis
Results
Patient characteristics
All RA n = 217 | Anti-CCP+ n = 178 | Anti-CCP- n = 39 | RF+ n = 154 | RF- n = 63 | Anti-CCP+/RF+ n = 147 | Anti-CCP-/RF- n = 32 | Controls n = 94 | |
---|---|---|---|---|---|---|---|---|
Age, yearsa | 51.5 (13.6) | 50.8 (13.2) | 55.0 (14.9) | 51.9 (13.3) | 50.8 (14.2) | 51.7 (13.6) | 55.0 (16.1) | 52.1 (9.2) |
Femaleb | 131 (60) | 109 (61) | 22 (56) | 91 (59) | 40 (63) | 86 (59) | 17 (53) | 57 (61) |
Ever-smokerb | 148 (68) | 122 (69) | 26 (67) | 109 (71) | 39 (62) | 103 (70) | 20 (62) | 60 (64) |
DASa | 3.5 (1.2) | 3.4 (1.1) | 4.0 (1.3) | 3.5 (1.2) | 3.5 (1.2) | 3.42 (1.1) | 3.9 (1.2) | NA |
DAS28a | 4.4 (1.2) | 4.4 (1.2) | 4.7 (1.2) | 4.5 (1.2) | 4.2 (1.3) | 4.5 (1.1) | 4.5 (1.1) | NA |
vdHSS totalc | 4.0 [1.5, 8.0] | 4.0 [1.5, 7.9] | 4.5 [2.0, 10] | 4.5 [2.0, 8.0] | 3.5 [1.5, 10] | 4.5 [2.0, 8.0] | 5.5 [1.8, 12.8] | NA |
vdHSS erosionc | 3.0 [1, 4.5] | 3.0 [1, 4.5] | 3.0 [1.0, 5.5] | 3.0 [1.5, 4.5] | 3.0 [1.0, 5.5] | 3.0 [1.0, 4.5] | 3.0 [1.0, 6.3] | NA |
vdHSS JSNc | 1.0 [0.0, 3.0] | 1.0 [0.0, 3.0] | 1.5 [0.0, 5.0] | 1.0 [0.0, 3.0] | 1.0 [0.0, 3.0] | 1.0 [0.0, 3.0] | 1.5 [0.0, 6.5] | NA |
Ultrasound grey scalec | 18 [10, 28] | 16 [9, 24] | 33 [20, 51] | 17 [10, 26] | 21 [12, 36] | 16 [9, 25] | 33 [21, 52] | NA |
Ultrasound power Dopplerc | 7 [3, 14] | 6 [2, 12] | 14 [6, 28] | 6 [2, 13] | 8 [3, 15] | 6 [2, 12] | 13 [6, 29] | NA |
Number of ACPA reactivitiesc | 9 [4, 12] | 10 [7, 12] | 0 [0, 1] | 10 [7, 12] | 2 [0, 10] | 10 [7, 12] | 0 [0, 1] | 0 [0, 0] |
ACPA reactivity status, n (%) | ||||||||
Fibβ 60-74cit | 162 (75) | 160 (90) | 2 (5) | 136 (88) | 26 (41) | 134 (91) | 0 (0) | 0 (0) |
Vim 60-75cit | 159 (73) | 152 (85) | 7 (18) | 130 (84) | 29 (46) | 128 (87) | 5 (16) | 5 (5) |
H4 31-50cit | 145 (67) | 142 (80) | 3 (8) | 119 (77) | 26 (41) | 118 (80) | 2 (6) | 1 (1) |
CEP-1 | 140 (65) | 137 (77) | 3 (8) | 117 (76) | 23 (37) | 115 (78) | 1 (3) | 1 (1) |
Fil 307-324cit | 136 (63) | 134 (75) | 2 (5) | 113 (73) | 23 (37) | 112 (76) | 1 (3) | 0 (0) |
Fibα 573cit | 123 (57) | 121 (68) | 2 (5) | 99 (64) | 24 (38) | 99 (67) | 2 (6) | 0 (0) |
Fibβ 36-52cit | 117 (54) | 116 (65) | 1 (3) | 96 (62) | 21 (33) | 96 (65) | 1 (3) | 2 (2) |
H3 1-30cit | 107 (49) | 106 (60) | 1 (3) | 93 (60) | 14 (22) | 92 (63) | 0 (0) | 0 (0) |
H4 14-34cit | 105 (48) | 103 (58) | 2 (5) | 90 (58) | 15 (24) | 88 (60) | 0 (0) | 3 (3) |
H3 21-44cit | 96 (44) | 94 (53) | 2 (5) | 80 (52) | 16 (25) | 79 (54) | 1 (3) | 1 (1) |
Fibα 621-635cit | 93 (43) | 92 (52) | 1 (3) | 78 (51) | 15 (24) | 77 (52) | 0 (0) | 1 (1) |
Vim 2-17cit | 88 (41) | 87 (49) | 1 (3) | 80 (52) | 8 (13) | 79 (54) | 0 (0) | 0 (0) |
Fibα 36-50cit | 79 (36) | 79 (44) | 0 (0) | 67 (44) | 12 (19) | 67 (46) | 0 (0) | 0 (0) |
Fibα 591cit | 69 (32) | 66 (37) | 3 (8) | 56 (36) | 13 (21) | 55 (37) | 2 (6) | 1 (1) |
Fibβ 74cit | 66 (30) | 60 (34) | 6 (15) | 54 (35) | 12 (19) | 51 (35) | 3 (9) | 3 (3) |
Fibβ 72cit | 27 (12) | 24 (13) | 3 (8) | 21 (14) | 6 (1) | 20 (14) | 2 (6) | 2 (2) |
ACPA reactivities and disease activity at baseline
ESR | CRP | DAS | SJC44 | RAI | US GS | US PD | vdHSS E | vdHSS JSN | vdHSS T | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
p
|
p
|
p
|
p
|
p
|
p
|
p
|
p
|
p
|
p
| ||||||||||||
Anti-CCP | + (82%) | 21 | 0.10 | 7 | 0.20 | 3.24 |
< 0.01
| 8 |
< 0.01
| 7 | 0.17 | 16 |
< 0.01
| 6 |
< 0.01
| 3 | 0.72 | 1 | 0.10 | 4 | 0.37 |
- (18%) | 13 | 7 | 4.09 | 18 | 8 | 33 | 14 | 3 | 1.5 | 4.5 | |||||||||||
Fibβ 60–74 | + (75%) | 20 | 0.63 | 7 |
0.04
| 3.28 |
0.02
| 7 |
< 0.01
| 7 | 0.65 | 17 |
< 0.01
| 6 |
< 0.01
| 3 | 0.97 | 1 | 0.71 | 4.5 | 0.73 |
- (25%) | 19 | 10 | 3.87 | 14 | 7 | 28 | 11 | 3 | 0.5 | 3.5 | |||||||||||
Vim 60–75 | + (73%) | 18 | 0.95 | 7 | 0.54 | 3.29 |
0.05
| 8 |
< 0.01
| 6 | 0.83 | 17 |
< 0.01
| 6 |
0.02
| 3 | 0.96 | 1 | 0.26 | 4.5 | 0.95 |
- (27%) | 21 | 7 | 3.77 | 14 | 7 | 23 | 9 | 3 | 1 | 4 | |||||||||||
H4 31–50 | + (67%) | 21 | 0.39 | 8 | 0.65 | 3.27 |
0.01
| 8 |
< 0.01
| 6 |
0.03
| 17 |
0.01
| 6 |
0.01
| 3 | 0.88 | 1 | 0.94 | 4.5 | 0.70 |
- (33%) | 17 | 7 | 3.84 | 13 | 10 | 21 | 9 | 3 | 0.75 | 3.25 | |||||||||||
CEP-1 | + (65%) | 21 | 0.13 | 8 | 0.93 | 3.32 | 0.35 | 9 | 0.06 | 7 | 0.47 | 17 |
0.03
| 6 | 0.12 | 3 | 0.76 | 1 | 0.46 | 4.5 | 0.54 |
- (35%) | 17 | 6 | 3.36 | 11 | 7 | 21 | 7 | 3 | 0.5 | 3.5 | |||||||||||
Fil 307–324 | + (63%) | 21 | 0.15 | 8 | 0.70 | 3.29 | 0.06 | 7 |
< 0.01
| 7 | 0.54 | 17 |
0.01
| 6 |
< 0.01
| 3 | 0.94 | 1 | 0.98 | 4 | 0.91 |
- (37%) | 17 | 7 | 3.64 | 13 | 7 | 21 | 9 | 3 | 1 | 4 | |||||||||||
Fibα 573 | + (57%) | 22 | 0.13 | 8 | 0.85 | 3.27 |
0.03
| 7 |
< 0.01
| 6 | 0.14 | 17 |
0.05
| 6 | 0.12 | 3 | 0.61 | 1 | 0.23 | 4.5 | 0.37 |
- (43%) | 16 | 7 | 3.42 | 12 | 8 | 21 | 8 | 3 | 0.5 | 4 | |||||||||||
Fibβ 36–52 | + (54%) | 21 | 0.08 | 8 | 0.78 | 3.26 |
0.05
| 8 |
< 0.01
| 6 | 0.06 | 17 | 0.06 | 6 |
0.03
| 3 | 0.58 | 1 |
0.05
| 4.5 | 0.19 |
- (46%) | 17 | 7 | 3.63 | 11 | 8 | 19 | 8 | 3 | 0.5 | 3.5 | |||||||||||
H3 1–30 | + (49%) | 18 | 0.97 | 7 | 0.40 | 3.29 | 0.48 | 8 | 0.09 | 6 | 1.00 | 17 |
0.04
| 6 | 0.09 | 3 | 0.62 | 0.5 |
0.04
| 4 | 0.16 |
- (51%) | 20 | 7 | 3.37 | 10 | 7 | 19 | 7 | 3 | 1 | 4.5 | |||||||||||
H4 14–34 | + (48%) | 21 | 0.13 | 8 | 0.74 | 3.27 | 0.28 | 7 |
< 0.01
| 7 | 0.77 | 17 | 0.30 | 7 | 0.86 | 3 | 0.39 | 1 | 0.30 | 4 | 0.28 |
- (52%) | 18 | 7 | 3.45 | 11 | 7 | 20 | 6 | 3 | 1 | 4.5 | |||||||||||
H3 21–44 | + (44%) | 22 | 0.09 | 9 | 0.21 | 3.31 | 0.69 | 9 | 0.07 | 7 | 0.84 | 17 | 0.28 | 6 | 0.41 | 3 | 0.68 | 0.5 | 0.14 | 4 | 0.32 |
- (56%) | 18 | 6 | 3.36 | 10 | 7 | 19 | 7 | 3 | 1 | 4.5 | |||||||||||
Fibα 621–635 | + (43%) | 22 | 0.36 | 8 | 0.84 | 3.29 | 0.09 | 7 |
< 0.01
| 7 | 0.54 | 16 |
0.02
| 6 | 0.07 | 2.5 | 0.46 | 0.5 | 0.30 | 4 | 0.34 |
- (57%) | 18 | 7 | 3.37 | 12 | 7 | 20 | 7 | 3 | 1 | 4.5 | |||||||||||
Vim 2–17 | + (41%) | 19 | 0.72 | 7 | 0.49 | 3.29 | 0.34 | 7 |
< 0.01
| 7 | 0.48 | 17 | 0.08 | 6 | 0.13 | 3 | 0.50 | 1 | 0.61 | 4 | 0.45 |
- (59%) | 20 | 7 | 3.36 | 11 | 7 | 20 | 7 | 3 | 1 | 4 | |||||||||||
Fibα 36–50 | + (36%) | 20 | 0.73 | 8 | 0.86 | 3.29 | 0.68 | 8 |
0.04
| 7 | 0.46 | 17 | 0.08 | 6 |
0.05
| 3 | 0.84 | 0.5 | 0.29 | 4 | 0.59 |
- (64%) | 19 | 7 | 3.41 | 11 | 7 | 19 | 7 | 3 | 1 | 4 | |||||||||||
Fibα 591 | + (32%) | 19 | 0.70 | 6 | 0.29 | 3.29 |
0.05
| 7 |
< 0.01
| 6 | 0.28 | 17 | 0.53 | 6 | 0.88 | 3 | 0.86 | 1 | 0.33 | 4.5 | 0.70 |
- (68%) | 20 | 8 | 3.40 | 11 | 7 | 19 | 7 | 3 | 0.5 | 4 | |||||||||||
Fibβ 74 | + (30%) | 22 | 0.19 | 8 | 0.87 | 3.25 | 0.53 | 9 | 0.12 | 8 | 0.74 | 17 | 0.08 | 6 | 0.67 | 2.5 | 0.57 | 0.5 | 0.32 | 4 | 0.48 |
- (70%) | 18 | 7 | 3.33 | 10 | 7 | 19 | 7 | 3 | 1 | 4 | |||||||||||
Fibβ 72 | + (12%) | 21 | 0.25 | 5 | 0.59 | 3.59 | 0.37 | 10 | 0.48 | 9 | 0.52 | 22 | 0.19 | 9 | 0.06 | 3 | 0.73 | 0.5 | 0.72 | 4 | 0.98 |
- (88%) | 19 | 7 | 3.31 | 9 | 7 | 17 | 6 | 3 | 1 | 4 |
ACPA reactivities and disease activity after initiation of DMARD treatment
Delta DAS 6 months | Delta DAS 12 months | Delta DAS 24 months | Delta US GS 12 months | Delta US GS 24 months | Delta US PD 12 months | Delta US PD 24 months | Delta vdHSS T 12 months | Delta vdHSS T 24 months | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
p
|
p
|
p
|
p
|
p
|
p
|
p
|
p
|
p
| |||||||||||
Fibβ 60–74 | + | −1.9 |
0.04
| −2.0 |
< 0.01
| − 2. 0 |
0.02
| − 12 |
< 0.01
| − 13 |
< 0.01
| −6 |
< 0.01
| − 6 |
< 0.01
| 0.5 | 0.92 | 1.0 | 0.69 |
– | − 2.5 | −2.6 | −2.6 | − 19 | −21 | −9 | −10 | 0.5 | 1.0 | ||||||||||
Vim 60–75 | + | −1.9 |
< 0.01
| − 1.9 |
< 0.01
| − 2.0 |
0.02
| − 12 |
< 0.01
| − 13 |
< 0.01
| − 6 | 0.06 | − 6 |
0.02
| 0.5 | 0.59 | 1.0 | 0.68 |
– | −2.6 | − 2.6 | − 2.6 | −17 | − 17 | −8 | −8 | 0.5 | 1.0 | ||||||||||
H4 31–50 | + | −1.9 |
< 0.01
| − 1.9 |
< 0.01
| −2.0 |
< 0.01
| − 12 |
0.05
| − 13 |
< 0.01
| − 6 | 0.08 | − 6 |
0.02
| 0.5 | 0.15 | 1.0 | 0.81 |
– | −2.5 | − 2.8 | − 2.7 | − 15 | −17 | −7 | −8 | 0.5 | 1.0 | ||||||||||
CEP-1 | + | −2.0 | 0.75 | − 2.1 | 0.79 | −2.1 | 0.48 | −12 | 0.23 | − 14 | 0.24 | −6 | 0.17 | −6 | 0.14 | 0.5 | 0.50 | 1.0 | 0.41 |
– | −2.1 | −2.2 | −2.0 | −14 | −14 | −7 | − 7 | 0.5 | 1.0 | ||||||||||
Fil 307–324 | + | −1.9 |
0.01
| −1.8 |
< 0.01
| − 1.9 |
0.01
| − 12 | 0.06 | − 13 |
0.01
| −6 |
0.03
| −5 |
0.01
| 0.5 | 0.75 | 1.0 | 0.76 |
– | −2.4 | −2.5 | −2.5 | −16 | −16 | −7 | − 7 | 0.5 | 1.0 | ||||||||||
Fibα 573 | + | −1.9 |
< 0.01
| −1.8 |
< 0.01
| − 1.9 |
< 0.01
| − 13 | 0.36 | − 14 | 0.12 | −6 | 0.21 | −6 | 0.08 | 0.5 | 0.89 | 1.0 | 0.77 |
– | −2.5 | −2.6 | −2.4 | −13 | −15 | −7 | −7 | 0.5 | 1.5 | ||||||||||
Fibβ 36–52 | + | −1.9 |
0.02
| −1.9 |
< 0.01
| − 1.9 |
< 0.01
| −12 | 0.23 | −14 | 0.09 | −6 | 0.08 | −5 |
0.02
| 0.5 | 0.89 | 1.0 | 0.58 |
– | −2.4 | −2.5 | −2.5 | −14 | − 14 | −7 | −7 | 0.5 | 1.5 | ||||||||||
H3 1–30 | + | −2.1 | 0.97 | − 2.2 | 0.97 | − 2.0 | 0.44 | −12 | 0.31 | − 13 |
0.04
| −6 | 0.25 | −6 | 0.09 | 0.5 | 0.24 | 1.0 | 0.45 |
– | −2.0 | −2.1 | −2.2 | −14 | −16 | −7 | −7 | 0.5 | 1.2 | ||||||||||
H4 14–34 | + | −1.9 | 0.07 | −2.0 | 0.12 | −2.0 | 0.14 | −12 | 0.46 | −12 |
0.02
| −7 | 0.63 | −6 | 0.54 | 0.5 | 0.32 | 1.5 | 0.10 |
– | −2.1 | −2.3 | −2.2 | −14 | −16 | −6 | −6 | 0.5 | 1.0 | ||||||||||
H3 21–44 | + | −2.0 | 0.48 | −2.0 | 0.31 | −2.0 | 0.37 | −12 | 0.29 | −13 | 0.39 | −6 | 0.28 | −6 | 0.38 | 0.5 | 0.39 | 1.5 | 0.76 |
– | −2.0 | −2.2 | −2.2 | −15 | −15 | −7 | −7 | 0.5 | 1.0 | ||||||||||
Fibα 621–635 | + | −1.7 |
0.04
| −1.8 |
0.04
| −1.9 |
0.03
| −11 |
0.02
| −13 |
0.01
| −6 | 0.09 | −6 |
0.05
| 0.5 | 0.20 | 1.0 | 0.22 |
– | −2.3 | −2.4 | −2.2 | −15 | −16 | −7 | −7 | 0.5 | 1.5 | ||||||||||
Vim 2–17 | + | −1.9 |
0.04
| −1.8 |
0.02
| −1.8 |
0.01
| −12 | 0.12 | −12 |
< 0.01
| −6 | 0.21 | −5 |
0.04
| 0.5 | 0.90 | 1.0 | 0.87 |
– | −2.2 | −2.3 | −2.3 | −14 | −16 | −7 | −7 | 0.5 | 1.0 | ||||||||||
Fibα 36–50 | + | −2.0 | 0.83 | − 2.0 | 0.74 | − 2.0 | 0.45 | −11 | 0.09 | − 12 | 0.10 | −5 |
0.02
| −5 |
0.02
| 0.5 | 0.61 | 1.0 | 0.52 |
– | −2.0 | −2.2 | −2.2 | −14 | −15 | −7 | −7 | 0.5 | 1.0 | ||||||||||
Fibα 591 | + | −1.9 | 0.08 | − 1.8 |
0.03
| − 1.8 |
0.01
| − 13 | 0.69 | − 16 | 0.70 | −6 | 0.84 | −6 | 0.77 | 0.5 | 0.41 | 1.0 | 0.58 |
– | −2.2 | −2.3 | −2.3 | −13 | −14 | −6 | −7 | 0.5 | 1.5 | ||||||||||
Fibβ 74 | + | −1.8 | 0.41 | −2.0 | 0.79 | −2.1 | 0.55 | −12 | 0.36 | −13 | 0.94 | −7 | 0.82 | −7 | 0.98 | 0.5 | 0.06 | 1.5 | 0.54 |
– | −2.1 | −2.2. | −2.0 | −13 | −14 | −6 | −6 | 0.5 | 1.0 | ||||||||||
Fibβ 72 | + | −2.0 | 0.84 | −2.0 | 0.73 | −1.9 | 0.78 | − 16 | 0.19 | − 17 | 0.21 | −7 | 0.13 | −9 | 0.11 | 0.2 | 0.98 | 0.5 | 0.51 |
– | −2.0 | −2.2. | −2.1 | −12 | −14 | −6 | −6 | 0.5 | 1.0 |
ACPA reactivities at baseline and prediction of treatment response
ACPA and radiographic damage
Number of ACPA reactivities | |||||
---|---|---|---|---|---|
0 n = 27 | 1–5 n = 39 | 6–8 n = 37 | ≥ 9 n = 114 |
p
value | |
vdHSS erosiona | 3.0 [1.0, 5.8] | 3.0 [1.5, 4.0] | 3.0 [2.0, 4.0] | 3.0 [1.0, 4.5] | 0.87 |
vdHSS joint space narrowinga | 1.5 [0.0, 4.8] | 0.5 [0.0, 2.0] | 0.5 [0.0, 3.0] | 1.0 [0.0, 3.8] | 0.54 |
vdHSS totala | 3.0 [1.5, 11.2] | 3.5 [1.5, 6.0] | 4.5 [2.5, 7.0] | 4.2 [1.5, 9.0] | 0.83 |
Erosive diseaseb | 15 (56) | 21 (54) | 21 (57) | 60 (53) | 0.97 |