Introduction
Patients and methods
Patients and data collection
Classification | Abbreviation | Definition/description |
---|---|---|
Original Bohan and Peter classification | PM | Primary polymyositis |
DM | Primary dermatomyositis | |
CTM | Myositis with another connective tissue disease | |
CAM | Myositis associated with cancer | |
Modified Bohan and Peter classification | PM | Pure polymyositis |
DM | Pure dermatomyositis | |
OM | Overlap myositis: with at least one clinical overlap featurea | |
CAM | Cancer-associated myositis: with clinical paraneoplasic featuresb | |
Novel clinicoserologic classification | PM | Pure polymyositis |
DM | Pure dermatomyositis | |
OM | Overlap myositis: with at least one clinical overlap feature and/or a myositis autoantibodyc | |
CAM | Cancer-associated myositis: with clinical paraneoplasic features and without a myositis autoantibody or anti-Mi-2 |
AIM classifications
Panel of 21 autoantibodies tested and screening strategy
Indirect immunofluorescence
Addressable laser bead immunoassay
Line immunoassay
Enzyme-linked immunosorbent assays
Anti-fibrillarin assay
Protein A assisted IPP
Statistical analyses
Results
Frequency of autoantibodies to 21 autoantigens
Frequency of anti-synthetases and SSc autoantibodies
Multiple myositis autoantibodies frequently coexist
Additional antibodiesa | Autoantibodies | Patients (total) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Ku (n = 23) | tRNA (n = 22) | U1RNP (n = 15) | Fibrillarin (n = 14) | PM-Scl (n = 9) | SSc (n = 9) | NUP (n = 3) | SRP (n = 2) | Ro (n = 31) | La (n = 14) | Mi-2 (n = 6) | No antibody (n = 20) | = 1 antibody (n = 80) | |
None | 7 (31) | 4 (18) | 6 (40) | 1 (7) | 2 (22) | 1 (11) | 2 (67) | 2 (100) | 4 (13) | 3 (21) | 3 (50) | 0 | 36 (36)b |
1 more | 7 (31) | 8 (36) | 6 (40) | 4 (28) | 4 (44) | 3 (33) | 1 (33) | 0 | 12 (39) | 4 (29) | 2 (33) | 0 | 26 (26) |
2 more | 5 (21) | 6 (28) | 2 (13) | 6 (43) | 1 (12) | 3 (33) | 0 | 0 | 10 (32) | 4 (29) | 0 | 0 | 12 (12) |
≥3 more | 4 (17) | 4 (18) | 1 (7) | 3 (22) | 2 (22) | 2 (23) | 0 | 0 | 5 (16) | 3 (21) | 1 (17) | 0 | 6 (6) |
Associations and exclusions between myositis autoantibodies
Ro | Ku | Jo-1 | PL-7 | PL-12 | KS | U1RNP | Fibrillarin | La | PM-Scl | Topo | RNAPOLIII | CENP-B | Th | Mi-2 | NUP | SRP | U5RNP | U2RNP | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n
| 31 | 23 | 15 | 5 | 1 | 1 | 15 | 14 | 14 | 9 | 3 | 2 | 2 | 2 | 6 | 3 | 2 | 1 | 1 |
Methods of detection | ALBIA | LIA, IPP | LIA, IPP, ALBIA | LIA, IPP | LIA, IPP | IPP | IPP, ALBIA | TNT, ALBIA | ALBIA, ELISA | LIA, IPP | ALBIA, ELISA | IPP, ELISA | ELISA, IIF | IPP | LIA, IPP | IPP | IPP | IPP | IPP |
Ro |
4
| 6 | 11 | 1 | 1 | 1 | 6 | 6 | 5 | 6 | 2 | - | 1 | 1 | - | - | - | - | - |
Ku | 6 |
7
| 4 | 1 | - | - | 2 | 8 | 4 | 2 | - | 1 | - | - | 1 | - | - | - | - |
Jo-1 | 11 | 4 |
2
| - | - | - | - | 2 | 3 | 1 | 2 | - | 1 | - | - | - | - | - | - |
PL-7 | 1 | 1 | - |
2
| - | - | - | 1 | 2 | - | - | - | - | - | - | - | - | - | - |
PL-12 | 1 | - | - | - |
-
| - | - | 1 | - | - | - | - | - | - | - | - | - | - | - |
KS | 1 | - | - | - | - |
-
| - | - | - | - | - | - | - | - | - | - | - | - | - |
U1RNP | 6 | 2 | - | - | - | - |
6
| 2 | 2 | - | - | - | - | 1 | - | - | - | - | 1 |
Fibrillarin | 6 | 8 | 2 | 1 | 1 | - | 2 |
1
| 2 | 1 | - | 1 | 1 | - | 1 | - | - | - | - |
La | 5 | 4 | 3 | 2 | - | - | 2 | 2 |
3
| 1 | 1 | - | - | - | 1 | 1 | - | - | 1 |
PM-Scl | 6 | 2 | 1 | - | - | - | - | 1 | 1 |
2
| 1 | - | - | - | 1 | - | - | - | - |
Topo | 2 | - | 2 | - | - | - | - | - | 1 | 1 |
-
| - | - | - | 1 | - | - | - | - |
RNAPOLIII | - | 1 | - | - | - | - | - | 1 | - | - | - |
-
| - | - | 1 | - | - | - | - |
CENP-B | 1 | - | 1 | - | - | - | - | 1 | - | - | - | - |
-
| - | - | - | - | - | - |
Th | 1 | - | - | - | - | - | 1 | - | - | - | - | - | - |
1
| - | - | - | - | - |
Mi-2 | - | 1 | - | - | - | - | - | 1 | 1 | 1 | 1 | 1 | - | - |
3
| - | - | - | - |
NUP | - | - | - | - | - | - | - | - | 1 | - | - | - | - | - | - |
2
| - | - | - |
SRP | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
2
| - | - |
U5RNP | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
1
| - |
U2RNP | - | - | - | - | - | - | 1 | - | 1 | - | - | - | - | - | - | - | - | - |
-
|
Anti-Ro, anti-Ro52, and anti-Ro60
Anti-Ku
Anti-fibrillarin
Anti-synthetases
Anti-Mi-2
Fine specificity of anti-Ku autoantibodies
Comparison of immunoassay sensitivities
Demographics, distribution of patients, and associated autoantibodies according to the modified Bohan and Peter classification at diagnosis
PM (n = 14) | DM (n = 23) | OM (n = 60) | CAM (n = 3) |
P
a
| |
---|---|---|---|---|---|
Age at diagnosis (years; mean ± SD) | 52.7 ± 16.8 | 45.4 ± 16.7 | 45.6 ± 13.5 | 56.3 ± 11 | 0.303 |
Mean follow-up period (years; mean ± SD) | 8.15 ± 4.8 | 12.52 ± 9.2 | 8.05 ± 6.1 | 7.64 ± 2.7 | 0.013 |
Associated autoantibodies | |||||
Anti-Ro (n = 31) | 4 (28.6) | 5 (21.7) | 22 (36.7) | 0 | 0.185 |
Anti-Ku (n = 23) | 3 (21.4) | 5 (21.7) | 15 (25) | 0 | 0.633 |
Anti-synthetases (n = 22) | 3 (21.4) | 4 (17.4) | 15 (25) | 0 | 0.463 |
Anti-U1RNP (n = 15) | 0 | 2 (8.7) | 13(21.7) | 0 | 0.024b |
Anti-fibrillarin (n = 14) | 0 | 1 (4.3) | 13 (21.7) | 0 | 0.007c |
Anti-La (n = 14) | 1 (7.1) | 3 (13) | 10 (16.7) | 0 | 0.394 |
SSc autoantibodies (n = 9) | 0 | 1 (4.3) | 8 (13.3) | 0 | 0.081 |
Anti-PM-Scl (n = 9) | 0 | 3 (13) | 6 (10) | 0 | 0.737 |
Anti-Mi-2-IPP (n = 3) | 0 | 2 (8.7) | 0 | 1 (33)d | - |
Anti-Mi-2-LIA (n = 3) | 0 | 0 | 3 (5) | 0 | - |
Anti-NUP (n = 3) | 1 (7.1) | 0 | 2 (3.3) | 0 | 1 |
Anti-SRP (n = 2) | 0 | 0 | 2 (3.3) | 0 | 0.515 |
None (n = 20) | 5(35.7) | 6 (26.1) | 7(11.7) | 2 (66) | 0.02e |
Impact of autoantibodies on myositis classification at diagnosis
Classifications | PM | DM | OM | CAM | Total |
---|---|---|---|---|---|
Original Peter and Bohan classification: previous studya | 45 | 28 | 24 | 3 | 100 |
Modified Peter and Bohan classification: previous study | 14 | 23 | 60 | 3 | 100 |
Novel clinicoserologic classification: previous studyb | 10 | 20 | 68 | 2 | 100 |
Novel clinicoserologic classification: present studyb | 7 | 8 | 82 | 3 | 100 |
Clinical features independently associated with AIM autoantibodies
Autoantibodies | Clinical featuresa | OR | 95% CI |
P
|
---|---|---|---|---|
Anti-Jo-1b | Interstitial lung disease | 14.5 | 3.52 to 59.78 | <0.001 |
Arthritis | 11.6 | 2.92 to 45.65 | <0.001 | |
Fever | 9.7 | 2.72 to 34.91 | <0.001 | |
Puffy hands | 9.6 | 2.82 to 32.92 | <0.001 | |
Associated CTD | 0.14 | 0.03 to 0.70 | 0.016 | |
Response to prednisone alone | 0.04 | 0.01 to 0.32 | 0.002 | |
Need for second line drug | 25.3 | 4.24 to 150 | <0.001 | |
Anti-fibrillarin | Raynaud's phenomenon | 10.9 | 2.83 to 42.60 | <0.001 |
Any lung involvement | 3.5 | 1.01 to 12.39 | 0.050 | |
Associated CTD | 4.1 | 1.14 to 14.50 | 0.031 | |
Anti-U1RNP | Raynaud's phenomenon | 9.8 | 2.28 to 42.59 | 0.002 |
Arthritis | 5.8 | 1.74 to 19.18 | 0.004 | |
Sclerodactily | 6.8 | 2.03 to 22.49 | 0.001 | |
Associated CTD | 6.8 | 1.76 to 26.55 | 0.006 | |
Associated SSc | 6.1 | 1.83 to 20.26 | 0.003 | |
Monophasic myositis course | 8.1 | 1.39 to 46.7 | 0.020 | |
SSc autoantibodies | Telangiectasias | 19.3 | 2.05 to 181.51 | 0.010 |
Sclerodactyly | 8.6 | 1.88 to 39.60 | 0.005 | |
Scleroderma proximal to MCP | 5.3 | 1.07 to 26.78 | 0.041 | |
Associated SSc | 5.8 | 1.29 to 25.78 | 0.022 | |
Anti-Ro or anti-Ro52 | Response to prednisone alone | 6.2 | 1.23 to 31.64 | 0.027 |
Need for second line drug | 0.12 | 0.03 to 0.54 | 0.006 |