Anti-MCV Antibodies Predict Radiographic Progression in Greek Patients with Very Early

Anti-MCV antibodies predict radiographic progression in Greek patients with very early (< 3months duration) rheumatoid arthritis.

Supplement Material

Clinical Rheumatology

Georgia Barouta1, Christina G Katsiari1, Ioannis Alexiou1, Christos Liaskos1, Areti Varna1, Dimitrios P. Bogdanos1, Anastasios Germenis2, Lazaros I. Sakkas1

Corresponding author:

Lazaros Sakkas

Department of Rheumatology and Clinical Immunology,

Faculty of Medicine, University of Thessaly and

University General Hospital of Larissa,

Biopolis 41 110, Larissa, Greece

Tel:+30-2413502813

Fax: +30-2413501016

Email:

Supplement Table 1. Demographic characteristics, clinical and laboratory features, radiological scores in early RA patients positive or negative for anti-CCP and RF.

Parameters / Anti-CCP (+)
Mean (±SD) / Anti-CCP (-)
Mean (±SD) / P* / RF (+)
Mean (±SD) / RF (-)
Mean (±SD) / P**
Age / 55.4 (±16.1) / 63.5 (±15.9) / 0.2 / 56.7 (±15.7) / 61.8 (±16.7) / 0.5
Gender (M:F) / (1:1) / (1:2) / 0.5 / 1:2 / 1:1 / 1.0
DD (mo) / 2.5 (±0.9) / 2.5 (±1.2) / 1.0 / 2.3 (±0.8) / 2.6 (±1.2) / 0.4
Smoking / 7 (58.3%) / 5 (33.3%) / 1.0 / 4 (40%) / 8 (47.1%) / 1.0
DAS28 t=0 / 6.3 (±1.1) / 6.5 (±0.9) / 0.6 / 5.9 (±0.9) / 6.6 (±1.0) / 0.08
DAS28 t=2y / 3.1 (±1.4) / 3.3 (±1.4) / 0.7 / 3.6 (±1.1) / 3.0 (±1.5) / 0.3
ESR (mm/h) t=0 / 51.7 (±22.9) / 46.1 (±23.0) / 0.6 / 50.3 (±21.7) / 47.5 (±23.8) / 0.8
ESR (mm/h) t=2y / 28.6 (±18.9) / 21.1 (±9.3) / 0.2 / 29.9 (±13.5) / 21.7 (±15.0) / 0.2
CRP (mg/dl) t=0 / 3.6 (±2.6) / 4.6 (±4.4) / 0.5 / 3.5 (±2.0) / 4.5 (±4.4) / 0.4
CRP (mg/dl) t=2y / 0.8 (±0.9) / 0.6 (±0.7) / 0.5 / 1.3 (±1.2) / 0.4 (±0.3) / 0.06
TJC (0-28) t=0 / 14 (±8) / 16 (±7) / 0.5 / 12.6 (±6.8) / 17.0(±7.8) / 0.2
TJC (0-28) t=2y / 2 (±4) / 4 (±6) / 0.3 / 2.8 ±( 4.3) / 3.6 (±5.7) / 0.7
SJC (0-28) t=0 / 10 (±8) / 11 (±7) / 0.8 / 6.8 (±6.0) / 12.4 (±7.6) / 0.06
SJC (0-28) t=2y / 2 (±3) / 1 (±2) / 0.7 / 2.1 (±2.9) / 1.3 (±1.6) / 0.5
Morn Stiff (min) t=0 / 106 (±99) / 130 (±101) / 0.5 / 94 (±59) / 135 (±116) / 0.3
Morn Stiff (min) t= 2y / 13 (±22) / 7 (±10) / 0.5 / 19(±24) / 5 (±7) / 0.1
Pain VAS t=0 / 60.4 (±13.8) / 62.7 (±10.9) / 0.7 / 58.0 (±15.8) / 63.8 (±9.0) / 0.3
Pain VAS t=2y / 24.2 (±14.4) / 25.0 (±17.6) / 0.9 / 27.8 (±14.0) / 22.9(±17.1) / 0.5
HAQ (0-3) t=0 / 1.5 (±0.7) / 1.7 (±0.7) / 0.5 / 1.3 (±0.7) / 1.8 (±0.6) / 0.09
HAQ (0-3) t=2y / 0.6 (±0.5) / 0.7 (±06) / 0.6 / 0.8 (±0.5) / 0.6 (±0.6) / 0.4
Anti-MCV (U/ml) / 271 (±361) / 51 (±63) / 0.1 / 317 (±376) / 49 (±67) / 0.06
Anti-CCP (U/ml) / - / - / - / 230 (±281) / 53 (±149) / 0.1
RF (U/ml) / 59 (±55) / 46 (±82) / 0.6 / - / - / -
Larsen score t=0 / 1.3 (±4.1) / 7.9 (±13.6) / 0.1 / 0.4 (±1.2) / 7.7 (±13.1) / 0.048
Larsen score t=2y / 6.2 (±5.6) / 12.1 (±13.7) / 0.2 / 5.6 (±2.8) / 11.3 (±13.1) / 0.1
ΔRo / 4.8 (±3.4) / 3.5 (±4.0) / 0.4 / 5.1 (±3.3) / 3.6 (±3.9) / 0.3
Ex-RA t=0 / 3 (25%) / 5 (33.3%) / 0.7 / 1 (10%) / 7 (41.2%) / 0.2
Ex-RA t=2y / 2 (16.7%) / 5 (33.3%) / 0.4 / 2 (20%) / 5 (29.4) / 1.0
Comorbidities / 1 (±1) / 2 (±2) / 0.2 / 1 (±1) / 2 (±1) / 0.08
Pts on Biologic Tx t=2y / 4 (33%) / 0 (0 %) / 0.03 / 2 (20%) / 2 (12%) / 0.6
Pts on Steroid Tx t=0 / 5 (41.7%) / 8 (53.3%) / 0.7 / 4 (40%) / 9 (52.9%) / 0.7
Pts on Steroid Tx t=2y / 0 (0.0) / 3 (21.4%) / 0.2 / 0 (0.0) / 3 (17.7%) / 0.5

SD: Standard Deviation , M: male, F: female, mo: months, y: years min: minutes, DD: Disease Duration, TJC: Tender Joints count, SJC: Swollen Joints Count, DAS-28: Disease Activity Score based on 28 examined joints, HAQ: Health Assessment Questionnaire, VAS: Visual Analogue Scale, Morn Stiff: morning stiffness, ΔRo: Difference in Larsen score between 2 years and baseline , Ex-RA: number of patients with Extra-articular Rheumatoid Arthritis manifestations

t=0: baseline assessment, t=2y: assessment at 2years, Pts: Patients, Tx: Treatment

*: p value derived from the comparison of anti-CCP positive and negative patients

**: p value derived from the comparison of RF positive and negative patients

Supplement Table 2. Frequency of anti-MCV, anti-CCP and RF autoantibodies in established RA, in other rheumatic diseases and in normal controls.

Disease (n) / Anti-MCV (+)
n (%) / Anti-CCP (+)
n (%) / RF(+)
n (%)
Established RA (141) / 72 (51.1) / 83 (58.9) / 93 (66.0)
PsA (22) / 1 (4.6) / 1 (4.6) / 0 (0.0)
Gout (10) / 0 (0.0) / 0 (0.0) / 0 (0.0)
Axial SpA (7) / 0 (0.0) / 0 (0.0) / 0 (0.0)
CPP arthritis (3) / 1 (33.3) / 1 (33.3) / 0 (0.0)
Sjogren’s Syndrome (3) / 1 (33.3) / 2 (66.7) / 3 (100)
SLE (2) / 0 (0.0) / 0 (0.0) / 2 (100)
Enteropathic (2) / 0 (0.0) / 1 (50) / 0 (0.0)
ANCA-Vasculitis (2) / 0 (0.0) / 0 (0.0) / 2 (100)
Sarcoidosis (1) / 0 (0.0) / 0 (0.0) / 1 (100)
Thyroid related arthritis (1) / 0 (0.0) / 0 (0.0) / 0 (0.0)
Healthy Controls (40) / 6 (15) / 5 (12.5) / 1 (2.5)

n= number of patients, PsA= Psoriatic Arthritis, SpA= Spondylarthritis, CPP= calcium pyrophosphate, SLE= Systemic Lupus Erythematosus

Supplement Table 3. Diagnostic value of anti-MCV antibodies in established RA

anti-MCV / Est. RA vs non-RA / Est. RA vs DC / Est. RA vs NC
AUC / 0.695 / 0.721 / 0.660
Sensitivity / 51% / 51% / 51%
Specificity / 90% / 94% / 85%
PPV / NPV / 88% / 55% / 96% / 42% / 92% / 33%
PLR / NLR / 5.28 / 0.54 / 9.02 / 0.52 / 3.4 / 0.57
Diagnostic OR / 9.74 / 17.39 / 5.91
anti-CCP
AUC / 0.769 / 0.783 / 0.751
Sensitivity / 59% / 59% / 59%
Specificity / 89% / 91% / 87.5%
PPV / NPV / 89% / 59% / 94% / 45% / 94% / 38%
PLR / NLR / 5.47 / 0.46 / 6.24 / 0.45 / 4.7 / 0.47
Diagnostic OR / 11.88 / 13.74 / 10.02
RF
AUC / 0.822 / 0.801 / 0.850
Sensitivity / 66% / 66% / 66%
Specificity / 90% / 85% / 97%
PPV / NPV / 91% / 64% / 92% / 48% / 99% / 45%
PLR / NLR / 6.82 / 0.38 / 4.37% / 0.40 / 26.38 / 0.35
Diagnostic OR / 18.08 / 10.90 / 75.56

AUC=area under the curve; PPV= positive predictive value, NPV= negative predictive value, PLR=positive likelihood ratio, NLR: negative likelihood ratio, OR= odds ratio, Est. RA: Established RA, DC: Disease Controls, NC: Normal Controls.
Supplement Table 4. Demographic characteristics, clinical and laboratory features, radiological scores between anti-MCV positive and anti-MCV negative established RA patients.

Parameters / Anti-MCV (+)
(n=72)
Mean (±SD) / Anti-MCV (-)
(n=69)
Mean (±SD) / P
Age / 61.6 (±10.1) / 60.2 (± 11.5) / 0.4
Gender (M:F) / 27/45 (1:2) / 16/53 (1:3) / 0.07
DD (y) / 12.6 (±10.4) / 9.2 (±8.7) / 0.037
Smoking / 32 (44.4%) / 18 (26.1%) / 0.034
DAS28 t=0 / 4.9 (±1.7) / 4.5 (±1.5) / 0.2
DAS28 t=2y / 3.7 (±1.5) / 3.9 (±1.7) / 0.6
ESR (mm/h) t=0 / 32.5 (±21.4) / 24.8 (±16.8) / 0.019
ESR (mm/h) t=2y / 27.3 (±17.8) / 25.9 (±19.1) / 0.7
CRP (mg/dl) t=0 / 2.1 (±3.1) / 1.1 (±2.0) / 0.027
CRP (mg/dl) t=2y / 1.0 (±1.7) / 1.2 (±3.0) / 0.7
TJC (0-28) t=0 / 10 (±8) / 8 (±8) / 0.2
TJC (0-28) t=2y / 5 (±7) / 7 (±9) / 0.1
SJC (0-28) t=0 / 6 (±7) / 4(±5) / 0.016
SJC (0-28) t=2y / 3 (±4) / 3 (±4) / 0.9
Morn stiff (min) t=0 / 44.9(±69.3) / 45 (±73.0) / 0.9
Morn stiff (min) t=2y / 27.7 (±71.5) / 30.8 (±68.7) / 0.8
Pain VAS (0-100mm) t=0 / 40.8 (±21.5) / 39.9 (±20.8) / 0.8
Pain VAS (0-100mm) t=2y / 28.0 (±19.9) / 29.2 (±20.8) / 0.7
HAQ (0-3) t t=0 / 1.4 (±0.9) / 1.0 (±0.9) / 0.012
HAQ (0-3) t=2y / 0.9 (±0.85) / 0.8 (±0.8) / 0.5
Anti-CCP (U/ml) / 341.0 (±252.5) / 37.5 (±82.3) / 0.00
RF (U/ml) / 441.0 (±698.8) / 62.3 (±149.2) / 0.00
Larsen score t=0 / 51.1 (±29.5) / 36.9 (±26.8) / 0.004
Larsen score t=2y / 55.4 (±29.3) / 37.6 (±27.6) / 0.001
ΔRo / 4.9 (±5.2) / 3.4 (±6.9) / 0.2
Ex-RA t=0 / 36 (50%) / 24 (34.8%) / 0.09
Ex-RA t=2y / 40 (58.8%) / 24 (36.9%) / 0.015
Comorbidities / 2.6 (±1.7) / 2.8 (±2.0) / 0.4
Pts on Biologic Tx t=0 / 23 (31.9%) / 17 (24.6%) / 0.4
Pts on Biologic Tx t=2y / 31 (51.7%) / 18 (28.6%) / 0.01
Pts on Steroid Tx t=0 / 26 (36.1%) / 21 (30.4%) / 0.6
Pts on Steroid Tx t=2y / 17 (28.3%) / 10 (15.9%) / 0.1

SD: Standard Deviation , M: male, F: female, mo: months, y: years min: minutes, DD: Disease Duration, TJC: Tender Joints count, SJC: Swollen Joints Count, DAS-28: Disease Activity Score based on 28 examined joints, HAQ: Health Assessment Questionnaire, VAS: Visual Analogue Scale, Morn Stiff: morning stiffness, ΔRo: Difference in Larsen score between 2 years and baseline , Ex-RA: number of patients with Extra-articular Rheumatoid Arthritis manifestations, t=0: baseline assessment, t=2y: assessment at 2years

Supplement Table 5. Demographic characteristics, clinical and laboratory features, radiological scores in established RA patients positive or negative for anti-CCP and RF.

Parameters / Anti-CCP (+) (n=83)
Mean (±SD) / Anti-CCP (-) (n=58)
Mean (±SD) / P* / RF (+)
(n=93)
Mean (±SD) / RF (-)
(n=48)
Mean (±SD) / P**
Age / 61.5 (±10.5) / 60.1 (±11.3) / 0.5 / 62.5 (±9.9) / 57.9 (±11.9) / 0.03
Gender (M:F) / 1:2 / 1:3 / 0.1 / 1:2 / 1:4 / 0.08
DD (y) / 11.8 (±9.8) / 9.6 (±9.5) / 0.2 / 12.1 (±10.0) / 8.5 (±8.7) / 0.03
Smoking / 35 (42.2%) / 15 (25.9%) / 0.05 / 36 (38.7%) / 14 (29.2%) / 0.4
DAS28 t=0 / 4.9 (±1.6) / 4.4 (±1.5) / 0.06 / 4.9 (±1.7) / 4.3 (±1.4) / 0.03
DAS28 t=2y / 3.8 (±1.5) / 3.8 (±1.7) / 0.8 / 3.9 (±1.5) / 3.7 (±1.7) / 0.5
ESR (mm/hour) t=0 / 30.7 (±19.9) / 25.9 (±19.0) / 0.1 / 31.0 (±20.0) / 24.3 (±18.3) / 0.05
ESR (mm/hour) t=2y / 27.0 (±17.5) / 25.9 (±19.6) / 0.8 / 28.6 (±18.3) / 23.3 (±18.4) / 0.1
CRP (mg/dl) t=0 / 1.9 (±3.0) / 1.1 (±2.1) / 0.06 / 1.8 (±2.8) / 1.2 (±2.3) / 0.2
CRP (mg/dl) t=2y / 1.0 (±1.5) / 1.2 (±3.2) / 0.6 / 1.0 (±1.5) / 1.3 (±3.4) / 0.6
TJC (0-28) t=0 / 9 (±8) / 9 (±8) / 0.6 / 9 (±8) / 10 (±8) / 0.7
TJC (0-28) t=2y / 5 (±7) / 7(±9) / 0.2 / 6 (±9) / 7 (±9 ) / 0.6
SJC (0-28) t=0 / 6 (±7) / 4 (±4) / 0.002 / 6(±7) / 3 (±3) / 0.00
SJC (0-28) t=2y / 3 (±4) / 3 (±4) / 0.8 / 4 (±5) / 3 (±4) / 0.2
Morn Stiff (min) t=0 / 48 (±75) / 40(±65) / 0.5 / 46 (±72) / 43(±70) / 0.8
Morn Stiff (min) t=2y / 29 (±71) / 30 (±68) / 1.0 / 25 (±64) / 37 (±79) / 0.4
Pain VAS t=0 / 41.1 (±20.7) / 39.3 (±21.8) / 0.6 / 40.8 (±21.6) / 39.5 (±20.4) / 0.7
Pain VAS t=2y / 28.0 (±19.9) / 29.4 (±21.0) / 0.7 / 28.4 (±20.2) / 28.9 (±20.7) / 0.9
HAQ (0-3) t=0 / 1.4 (±0.8) / 1.0 (±0.8) / 0.002 / 1.3 (±0.8) / 1.0 (±0.8) / 0.06
HAQ (0-3) t=2y / 0.9 (±0.8) / 0.8 (±0.9) / 0.8 / 0.9 (±0.9) / 0.8 (±0.8) / 0.6
Anti-MCV (U/ml) / 442 (±486) / 16 (±17) / 0.00 / 385 (±474) / 37 (±156) / 0.00
RF (U/ml) / 394 (±662) / 56 (±152) / 0.00 / - / - / -
Anti-CCP (U/ml) / - / - / - / 276 (±257) / 31.5 (±79) / 0.00
Larsen score t=0 / 50.1 (±28.0) / 35.6 (±28.5) / 0.004 / 51.7 (±30.2) / 29.4 (±19.9) / 0.00
Larsen score t=2y / 53.1 (±27.6) / 37.2 (±30.2) / 0.004 / 54.1 (±29.5) / 33.1 (±25.3) / 0.00
ΔRo / 4.6 (±5.0) / 3.6 (±7.4) / 0.4 / 4.3 (±4.5) / 3.8 (±8.2) / 0.7
Ex-RA t=0 / 41 (49.4%) / 19 (32.8%) / 0.06 / 49 (52.7) / 11 (22.9%) / 0.001
Ex-RA t=2y / 45 (57.7%) / 19 (34.5%) / 0.01 / 53 (60.9%) / 11 (23.9%) / 0.00
Comorbidities / 3 (±2) / 3 (±2) / 0.7 / 3 (±2) / 3 (±2) / 0.9
Pts on Biologic Tx t=0 / 27 (32.5%) / 13 (22.4%) / 0.25 / 28 (30.1%) / 12 (25.0%) / 0.6
Pts on Biologic Tx t=2y / 36 (51.4%) / 13 (24.5%) / 0.003 / 35 (45.5%) / 14 (30.4%) / 0.1
Pts on Steroid Tx t=0 / 31 (37.4%) / 16 (27.6%) / 0.3 / 33 (35.5%) / 14 (29.2%) / 0.6
Pts on Steroid Tx t=2y / 18 (25.7%) / 9 (17.0%) / 0.3 / 21 (27.3%) / 6 (13.0%) / 0.07

SD: Standard Deviation, M: male, F: female, mo: months, y: years, min: minutes, DD: Disease Duration, TJC: Tender Joints count, SJC: Swollen Joints Count, DAS-28: Disease Activity Score based on 28 examined joints, HAQ: Health Assessment Questionnaire, VAS: Visual Analogue Scale, Morn Stiff: morning stiffness, ΔRo: Difference in Larsen score between 2 years and baseline, Ex-RA: number of patients with Extra-articular Rheumatoid Arthritis manifestations

t=0: baseline assessment, t=2y: assessment at 2years, Pts: Patients, Tx: Treatment

*: p value derived from the comparison of anti-CCP positive and negative patients

**: p value derived from the comparison of RF positive and negative patients