Background
Methods
Patients and muscle biopsies
Patient ID | Diagnosis | Age (years) | Gender | Disease duration (months) | Cumulative cortisone (mg) | Imuunosuppressive treatment at second biopsy | Autoantibodies | Support for diagnosis | MMT-8 (%) | s-CK (μcat/L) | HAQ (0.0–3.0) | FI-2 (%) | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
B | A | B | A | B | A | B | A | |||||||||
1 | DM | 40 | M | 3 | 14450.0 | Pred, AZA | MDA5, SSA, Ro60 | MW, S, LD | 87.5 | 87.5 | 1.3 | 1.1 | 1.13 | 0.75 | 21.7 | 27.4 |
2 | PM | 73 | F | 12 | 6222.5 | Pred, MTX | Neg | MW, CK, MB | 85.0 | 85.0 | 10.2 | 1.5 | 0.5 | 0.88 | 18.3 | 19.1 |
3 | DM | 69 | F | 2 | 10017.5 | Pred, MTX | ANA, TIF1γ | MW, CK, S, EMG | 81.4 | 91.3 | 29.3 | 1.0 | 0.63 | 0 | 0 | 11.2 |
4 | DM | 63 | M | 0.5 | 7330.0 | Pred, AZA | Neg | MW, CK, S, EMG | 78.8 | 90.0 | 48.2 | 1.0 | 0,38 | 0 | 86.2 | 100.0 |
5 | DM | 45 | F | 16 | 6842.5 | Pred, MTX | ANA, Mi-2 | MW, CK, MB, S, EMG | 98.8 | 87.5 | 43.0 | 2.1 | 1.5 | 0.88 | 17.3 | 25.3 |
6 | PM | 71 | F | 12 | 8415.0 | Pred, AZA | Neg | MW, CK, MB | 75.7 | 100 | 9.0 | 3.9 | 1.25 | 1.88 | NA | 17 |
Clinical and laboratory assessment
Histopathological and immunohistochemical analyses
RNA expression profiling
Western blot
Statistical analyses
Results
Effects of treatment on clinical parameters
Histopathological and immunohistochemical changes in pre- and post- treatment muscle biopsies
Effects of treatment on the overall gene expression
Effects on genes associated with immune response and inflammation
Gene symbol | Gene | Affy # | Fold change |
p
|
---|---|---|---|---|
Immune response and antigen presentation | ||||
CCL2 |
chemokine (C-C motif) ligand 2
| 216598_s_at | –5.9 | 0.004 |
CCL5 |
chemokine (C-C motif) ligand 5
| 1405_i_at | –3.0 | 0.043 |
CCR2 |
chemokine (C-C motif) receptor 2
| 206978_at | –2.3 | 0.004 |
CCR5 |
chemokine (C-C motif) receptor 5
| 206991_s_at | –2.8 | 0.027 |
CD52 |
CDW52 antigen (CAMPATH-1 antigen)
| 204661_at | –2.7 | 0.037 |
CD80 |
CD80 antigen (CD28 ag ligand 1, B7-1 ag)
| 1554519_at | –2.2 | 0.034 |
CD86 |
CD86 antigen (CD28 ag ligand 2, B7-2 ag)
| 210895_s_at | –2.6 | 0.013 |
CHRNA1 |
cholinergic receptor, nicotinic, αpolypeptide 1
| 206633_at | –2.8 | 0.028 |
CNPY3 |
trinucleotide repeat containing 5
| 1556389_at | –2.1 | 0.022 |
CPM |
carboxypeptidase M
| 206100_at | 2.2 | 0.028 |
HLA-DQB1 |
MHC class II, DQβ2
| 212998_x_at | –2.0 | 0.033 |
HLA-A |
major histocompatibility complex, class I, A
| 215313_x_at | –2.2 | 0.012 |
HLA-G |
HLA-G histocompatibility antigen, class I, G
| 211530_x_at | –2.3 | 0.010 |
HLA-C |
MHC class I, C
| 208812_x_at | –2.2 | 0.013 |
HLA-B |
MHC class I, B
| 209140_x_at | –2.2 | 0.017 |
HLA-F |
MHC class I, F
| 204806_x_at | –2.6 | 0.018 |
HLA-DQA1 |
MHC class II, DQα1
| 203290_at | –2.6 | 0.036 |
HLA-DQB1 |
MHC class II, DQβ1
| 209823_x_at | –2.8 | 0.010 |
HLA-DPA1 |
MHC class II, DPα1
| 213537_at | –2.9 | 0.009 |
IL-23A |
Interleukin 23, subunit alpha
| 217328_at | –5.2 | 0.005 |
IL-12RB1 |
Interleukin 12 receptor, beta 1
| 1552584_at | –2.1 | 0.020 |
NMU |
Neuromedin U
| 206023_at | 2.8 | 0.028 |
MMP3 |
Matrix metalloproteinase 3
| 205828_at | 10.7 | 0.023 |
IFN pathway | ||||
STAT1 |
signal transducer & activator of transcription 1, 91 kDa
| 209969_s_at | –3.3 | 0.008 |
CXCL10 |
chemokine (C-X-C motif) ligand 10
| 204533_at | –5.6 | 0.020 |
CXCL11 |
chemokine (C-X-C motif) ligand 11
| 211122_s_at | –5.6 | 0.015 |
RTP4 |
28kD interferon responsive protein
| 219684_at | –5.7 | 0.028 |
IRF8 |
IFN consensus sequence binding protein 1
| 204057_at | –2.4 | 0.033 |
ISG20 |
IFN stimulated gene 20 kDa
| 204698_at | –5.8 | 0.029 |
IFI6 |
IFNα-inducible protein
| 204415_at | –4.7 | 0.045 |
IFI30 |
IFNγ-inducible protein 30
| 201422_at | –2.2 | 0.036 |
IFI35 |
IFN -induced protein 35
| 209417_s_at | –2.6 | 0.036 |
IFIT3 |
IFN -induced protein w tetratricopeptide repeats 4
| 229450_at | –5.1 | 0.032 |
IRF9 |
IFN -stimulated transcription factor 3, γ
| 203882_at | –3.8 | 0.005 |
GBP1 |
guanylate binding protein 1, IFN-inducible
| 202269_x_at | –2.9 | 0.009 |
GBP2 |
guanylate binding protein 1, IFN-inducible
| 242907_at | –2.7 | 0.005 |
GBP5 |
guanylate binding protein 5
| 238581_at | –2.1 | 0.017 |
Inflammasome | ||||
AIM2 |
absent in melanoma 2
| 206513_at | –2.5 | 0.008 |
CASP1 |
caspase 1, (interleukin 1β convertase)
| 211367_s_at | –2.3 | 0.009 |
IL18 |
interleukin 18 (IFNg-inducing factor)
| 206295_at | –2.2 | 0.042 |
Eicosanoids | ||||
PTGER3 |
prostaglandin E receptor 3 (subtype EP3)
| 210832_x_at | 3.0 | 0.013 |
PTGER4 |
prostaglandin E receptor 4 (subtype EP4)
| 204897_at | –2.0 | 0.027 |
CYSLTR1 |
cysteinyl leukotriene receptor 1
| 230866_at | –2.8 | 0.037 |
Effects on genes involved in muscle tissue remodeling
Gene symbol | Gene | Affy # | Fold change |
p
|
---|---|---|---|---|
Ubiquitin proteasome pathway | ||||
PSMB8 |
proteasome subunit,β type, 8 (large multifunctional protease 7)
| 209040_s_at | –6.6 | 0.003 |
UBE2L6 |
ubiquitin-conjugating enzyme E2L 6
| 201649_at | –2.8 | 0.032 |
PSMB9 |
proteasome (prosome, macropain) subunit, beta type, 9
| 204279_at | –2.4 | 0.005 |
PSME1 |
proteasome) activator subunit 1 (PA28 α)
| 200814_at | –2.3 | 0.007 |
PSME2 |
proteasome activator subunit 2 (PA28β)
| 201762_s_at | –2.0 | 0.012 |
CNTN3 |
ubiquitin-activating enzyme E1C (UBA3 homolog, yeast)
| 229831_at | 2.4 | 0.029 |
Structure proteins and tissue remodeling | ||||
MYBPH |
myosin binding protein H
| 206304_at | –6.9 | 0.036 |
RRAD |
Ras-related associated with diabetes
| 204803_s_at | –3.2 | 0.013 |
BMP1 |
bone morphogenetic protein 1
| 207595_s_at | –2.7 | 0.001 |
NCOA6 |
Nuclear receptor co-activator
| 1568874_at | –3.0 | 0.041 |
CACNA1D |
calcium channel, voltage-dependent, L type, alpha 1D subunit
| 1555993_at | –2.9 | 0.035 |
CHST11 |
carbohydrate (chondroitin 4) sulfotransferase 11
| 226368_at | –2.1 | 0.009 |
MYH4 |
myosin, heavy polypeptide 4, skeletal muscle
| 208148_at | 2.2 | 0.020 |
FOXO1 |
forkhead box O1A
| 202723_s_at | 2.3 | 0.026 |
MSTN |
growth differentiation factor 8
| 207145_at | 2.3 | 0.041 |
VCL |
vinculin
| 200930_s_at | 2.4 | 0.022 |
TIMP4 |
tissue inhibitor of metalloproteinase 4
| 206243_at | 2.6 | 0.024 |
FKBP5 |
FK506 binding protein 5
| 204560_at | 3.4 | 0.015 |
ACTN3 |
actinin, alpha 3
| 206891_at | 3.4 | 0.037 |
Effects on genes involved in lipid metabolism
Gene symbol | Gene | Affy # | Fold change |
p
|
---|---|---|---|---|
Lipid transport and uptake | ||||
FABP7 |
fatty acid binding protein 7, brain
| 205029_s_at | 10.0 | 0.002 |
ABCD2 |
ATP-binding cassette, sub-family D member 2
| 207583_at | 4.55 | 0.043 |
APOL6 |
apolipoprotein L, 6
| 241869_at | –3.12 | 3.14E-05 |
Lipid accumulation and lipolysis | ||||
SCD |
stearoyl-CoA desaturase (delta-9)
| 223839_s_at | 3.86 | 0.042 |
CIDEC |
cell death-inducing DFFA-like effector c
| 219398_at | 3.53 | 0.049 |
CERS3 |
ceramide synthase 3
| 1554252_a_at | 3.2 | 0.021 |
CES1 |
carboxylesterase 1
| 209616_s_at | 2.98 | 0.028 |
MSTN |
myostatin
| 207145_at | 2.28 | 0.041 |
CNR1 |
Human CB1 cannabinoid receptor
| 213436_at | 2.14 | 0.009 |
LPL |
lipoprotein lipase
| 203549_s_at | 2.05 | 0.022 |
LIPE |
lipase, hormone-sensitive
| 213855_s_at | 2.00 | 0.034 |
ACSL3 |
fatty-acid-Coenzyme A ligase, long-chain 3
| 236168_at | –3.87 | 0.048 |
LSDP5 |
Lipid Storage Droplet Protein 5
| 1560457_x_at | –2.61 | 0.030 |
SPHK1 |
sphingosine kinase 1
| 219257_s_at | –2.20 | 0.037 |