Table 1. Characteristics of SLE patients and healthy controls (mean ± SD, %).
Characteristic
|
SLE
|
Control
|
P value
|
Cases
|
N = 74
|
N = 54
|
|
Number of males/females
|
3/71
|
3/51
|
NS
|
Age (year)
|
31.42 ± 12.02
|
27.1 ± 8.1
|
NS
|
Disease duration (month)
|
49.13 ± 9.331
|
-
|
|
Clinical features
|
|
|
|
SLEDAI≥10
|
43
|
-
|
|
Lupus nephritis
|
48
|
-
|
|
Raynaud’s phenomenon
|
27
|
-
|
|
Malar rash
|
32
|
-
|
|
Fever
|
47
|
-
|
|
Oral ulcer
|
16
|
-
|
|
Arthritis
|
35
|
-
|
|
Serositis
|
32
|
-
|
|
Neurological disorder
|
18
|
-
|
|
Interstitial lung
|
17
|
-
|
|
Laboratory findings
|
|
|
|
Anti-dsDNA(+)
|
54
|
-
|
|
Anti-SmD1(+)
|
60
|
-
|
|
Anti-U1snRNP(+)
|
47
|
-
|
|
Anti-SSA60(+)
|
55
|
-
|
|
Anti-SSA52(+)
|
27
|
-
|
|
Anti-SSB(+)
|
25
|
-
|
|
C3↓
|
78
|
-
|
|
C4↓
|
68
|
-
|
|
IgA↑
|
60
|
-
|
|
IgG↑
|
59
|
-
|
|
Values are number (%) of patients unless indicate otherwise.
NS, No significance; SLE, systemic lupus erythematosus. SLEDAI, SLE Disease Activity Index; Anti-SmD1, Anti-Smith D1; Anti-dsDNA, Anti-double-stranded DNA; Anti-U1snRNP, Anti-U1 small nuclear ribonucleoprotein; Anti-SSA, Anti- Sjögren syndrome antigen A; Anyi-SSB, Anti-Sjögren syndrome antigen B; C3/C4, complement component 3/4; IgG/IgM/IgA, immunoglobulin G/M/A.
Table 2. Correlation of the frequencies of PC, SM, NSM, DN and N B cells in SLE patients with SLEDAI or biochemical indices.
Laboratory test parameters
|
Cases
|
PC B cells
r
|
SM B cells
r
|
NSM B cells
r
|
DN B cells
r
|
N B cells
r
|
SLEDAI
|
74
|
0.03501
|
0.08304*
|
0.01213
|
0.00436
|
-0.0845*
|
Amounts of proteinuria (g/24 h)
|
69
|
-0.01255
|
0.01846
|
0.09926*
|
-0.02297
|
-0.03198
|
Immunoglobulin G (g/L)
|
74
|
0.02445
|
0.07461*
|
0.08158*
|
0.05188
|
-0.2087*
|
Immunoglobulin A (g/L)
|
74
|
0.06296
|
0.03587
|
0.1280
|
-0.1827
|
-0.04001
|
Immunoglobulin M (g/L)
|
74
|
0.09914*
|
-0.02337*
|
-0.07387*
|
0.005707
|
-0.02223
|
Complement 3 (g/L)
|
74
|
0.1162*
|
0.006449
|
0.03364
|
0.001436
|
-0.06764
|
Complement 4 (g/L)
|
74
|
-0.1857
|
0.1340
|
0.09826
|
-0.1698
|
0.00045
|
DN, double negative; naïve; NSM, non-switched memory; PC, plasmablast cells; SLE, systemic lupus erythematosus; SLEDAI, SLE Disease Activity Index; SM, switched memory.
*P ﹤ 0.05.
Table 3. Association between the percentages of PC, SM, NSM, DN and N B cells and the clinic-pathological parameters in SLE patients (mean ± SD, %).
Parameters
|
|
Cases
|
PC Bcells (%)
|
P value
|
SM B cells (%)
|
P value
|
NSM B cells (%)
|
P value
|
DN B cells (%)
|
P value
|
NB cells (%)
|
P value
|
Anti-dsDNA
|
+
|
44
|
7.799
±0.9774
|
0.300
|
19.54
±1.208
|
0.896
|
16.43
±2.100
|
0.641
|
12.04
±1.612
|
0.084
|
50.35
±3.049
|
0.198
|
|
-
|
30
|
6.449
±0.626
|
|
19.88
±2.527
|
|
14.97
±2.196
|
|
43.99
±3.049
|
|
50.35±
3.880
|
|
Anti-histones
|
+
|
26
|
8.536
±1.167
|
0.138
|
24.15
±2.613
|
0.007
|
17.52
±3.652
|
0.420
|
13.90
±2.231
|
0.017
|
35.85
±4.009
|
0.001
|
|
-
|
48
|
6.556
±0.739
|
|
17.26
±1.169
|
|
14.92
±1.297
|
|
8.729
±1.002
|
|
52.37
±2.692
|
|
Anti-smD1
|
+
|
45
|
7.919
±0.929
|
0.193
|
20.32±1.549
|
0.522
|
16.31
±2.045
|
0.702
|
11.07
±1.399
|
0.537
|
44.20
±3.164
|
0.225
|
|
-
|
29
|
6.216
±0.718
|
|
18.68
±2.082
|
|
15.10
±2.293
|
|
9.735
±1.587
|
|
50.23
±3.669
|
|
Anti-U1snRNP
|
+
|
35
|
7.856
±1.176
|
0.371
|
20.30
±1.854
|
0.641
|
14.95
±1.662
|
0.586
|
11.82
±1.717
|
0.253
|
44.87
±3.594
|
0.508
|
|
-
|
39
|
6.709
±0.5865
|
|
19.13
±1.684
|
|
16.63
±2.497
|
|
9.406
±1.255
|
|
48.09
±3.269
|
|
Anti-nucleo
|
+
|
35
|
7.625
±0.954
|
0.571
|
18.42
±1.839
|
0.326
|
14.12
±2.425
|
0.277
|
12.28
±1.807
|
0.108
|
47.52
±3.960
|
0.704
|
|
-
|
39
|
6.898
±0.853
|
|
20.87
±1.675
|
|
17.46
±1.879
|
|
8.904
±1.075
|
|
45.67
±2.870
|
|
Anti-SSA60
|
+
|
41
|
7.151
±0.679
|
0.832
|
21.38
±1.710
|
0.062
|
16.74
±2.194
|
0.424
|
11.60
±1.399
|
0.173
|
53.01
±3.811
|
0.049
|
|
-
|
33
|
7.437
±1.323
|
|
16.54
±1.428
|
|
14.17
±1.570
|
|
8.596
±1.458
|
|
43.08
±2.999
|
|
Anti-SSA52
|
+
|
20
|
7.444±1.179
|
0.856
|
24.30
±3.274
|
0.022
|
23.26
±4.333
|
0.02
|
8.155
±1.205
|
0.167
|
50.18
±2.671
|
0.013
|
|
-
|
54
|
7.180
±0.759
|
|
17.9
±1.131
|
|
13.09
±1.172
|
|
11.43
±1.356
|
|
36.82
±4.695
|
|
Anti-SSB
|
+
|
15
|
6.865
±1.446
|
0.761
|
21.24
±3.548
|
0.530
|
22.85
±5.868
|
0.019
|
9.406
±1.879
|
0.587
|
39.57
±6.199
|
0.145
|
|
-
|
59
|
7.350
±0.713
|
|
19.28
±1.283
|
|
14.05
±1.137
|
|
10.83
±1.231
|
|
48.34
±2.559
|
|
Anti-P0
|
+
|
30
|
7.653
±1.066
|
0.605
|
17.26
±1.560
|
0.108
|
12.82
±1.146
|
0.103
|
11.78
±1.774
|
0.334
|
50.24
±3.656
|
0.210
|
|
-
|
44
|
6.978
±0.791
|
|
21.33
±1.767
|
|
17.90
±2.408
|
|
9.704
±1.287
|
|
44.06
±3.176
|
|
LN
|
Yes
|
36
|
6.569
±0.657
|
0.299
|
20.07
±2.042
|
0.761
|
17.65
±2.414
|
0.250
|
10.70
±1.567
|
0.889
|
44.98
±3.355
|
0.525
|
|
No
|
38
|
7.898
±1.067
|
|
19.31
±1.474
|
|
14.12
±1.886
|
|
10.40
±1.425
|
|
48.07
±3.481
|
|
Malar rash
|
Yes
|
24
|
9.554
±1.404
|
0.011
|
25.54
±2.717
|
0.001
|
15.96
±2.656
|
0.957
|
10.92
±1.755
|
0.807
|
38.00
±4.333
|
0.013
|
|
No
|
50
|
6.146
±0.607
|
|
16.87
±1.111
|
|
15.78±1.883
|
|
10.36
±1.316
|
|
50.68
±2.743
|
|
Arthritis
|
Yes
|
26
|
6.391
±0.694
|
0.322
|
18.61
±2.247
|
0.529
|
13.95
±1.137
|
0.367
|
8.935
±1.429
|
0.261
|
52.08
±3.650
|
0.093
|
|
No
|
48
|
7.718
±0.902
|
|
20.26
±1.488
|
|
16.86
±2.267
|
|
11.42
±1.415
|
|
43.58
±3.089
|
|
Serositis
|
Yes
|
18
|
6.234
±1.018
|
0.368
|
18.57
±2.465
|
0.615
|
11.14
±1.003
|
0.081
|
9.713
±1.915
|
0.655
|
54.32
±4.281
|
0.068
|
|
No
|
56
|
7.579
±0.772
|
|
20.04
±1.445
|
|
17.35±
1.953
|
|
10.81
±1.250
|
|
44.07
±2.812
|
|
Interstitial lung
|
Yes
|
13
|
6.985
±1.018
|
0.848
|
20.25
±2.737
|
0.834
|
11.78
±1.163
|
0.222
|
9.840
±2.703
|
0.758
|
51.09
±4.689
|
0.390
|
|
No
|
61
|
7.308
±0.742
|
|
19.56
±1.397
|
|
16.70
±1.819
|
|
10.70
±1.145
|
|
45.60
±2.748
|
|
Anti-SmD1, anti-Smith D1; Anti-dsDNA, Anti-double-stranded DNA; Anti-U1snRNP, Anti- U1 small nuclear ribonucleoprotein; Anti- nucleo, Anti-nucleosomes, Anti-SSA, Anti- Sjögren syndrome antigen A; Anyi-SSB, Anti-Sjögren syndrome antigen B ,Anti-P0, anti-ribosomal P0 antibody ;DN, double negative; LN, lupus nephritis; N, naïve; NSM, non-switched memory; PC, plasmablast cells; SLE, systemic lupus erythematosus; SM, switched memory.
Table 4. Association between the percentage of PD-1+B cells and clinic-pathological parameters in SLE patients (mean ± SD, %).
Parameters
|
|
Cases
|
PD-1+B cells (%)
|
P
|
Anti-dsDNA
|
+
|
44
|
12.96±2.023
|
0.040
|
|
-
|
30
|
8.109±1.060
|
|
Anti-histone
|
+
|
26
|
15.03±2.454
|
0.025
|
|
-
|
48
|
10.22±0.798
|
|
Anti-smD1
|
+
|
45
|
13.06±1.834
|
0.373
|
|
-
|
29
|
11.17±1.220
|
|
Anti-U1snRNP
|
+
|
35
|
12.53±1.617
|
0.571
|
|
-
|
39
|
11.35±1.326
|
|
Anti-nucleo
|
+
|
35
|
12.21±1.397
|
0.766
|
|
-
|
39
|
11.59±1.540
|
|
Anti-SSA60
|
+
|
41
|
12.82±1.459
|
0.234
|
|
-
|
33
|
10.23±1.128
|
|
Anti-SSA52
|
+
|
20
|
15.25±2.829
|
0.048
|
|
-
|
54
|
10.67±0.9151
|
|
Anti-SSB
|
+
|
15
|
13.47±2.930
|
0.451
|
|
-
|
59
|
11.52±1.066
|
|
Anti-P0
|
+
|
30
|
11.03±1.294
|
0.486
|
|
-
|
44
|
12.51±1.498
|
|
C3↓
|
Yes
|
58
|
12.21±1.475
|
0.881
|
|
No
|
16
|
11.83±1.256
|
|
IgG↑
|
Yes
|
44
|
12.52±1.686
|
0.621
|
|
No
|
30
|
11.47±1.305
|
|
Lupus nephritis
|
Yes
|
36
|
15.55±1.912
|
<0.0001
|
|
No
|
38
|
8.468±0.386
|
|
Malar rash
|
Yes
|
24
|
14.08±2.459
|
0.146
|
|
No
|
50
|
10.87±0.956
|
|
Fever
|
Yes
|
35
|
12.14±1.584
|
0.838
|
|
No
|
39
|
11.71±1.363
|
|
Oral ulcer
|
Yes
|
12
|
16.49±3.818
|
0.049
|
|
No
|
62
|
11.02±0.964
|
|
Arthritis
|
Yes
|
26
|
12.10±1.937
|
0.895
|
|
No
|
48
|
11.81±1.210
|
|
Serositis
|
Yes
|
18
|
9.87±1.491
|
0.265
|
|
No
|
56
|
12.57±9.501
|
|
Interstitial lung
|
Yes
|
13
|
9.503±1.869
|
0.283
|
|
No
|
61
|
12.42±1.181
|
|
Anti-SmD1,anti-Smith D1,Anti-dsDNA, Anti-double-stranded DNA; Anti-U1snRNP,Anti- U1 small nuclear ribonucleoprotein; Anti-nucleo, Anti-nucleosomes, Anti-SSA, Anti- Sjögren syndrome antigen A; Anti-SSB, Anti-Sjögren syndrome antigen B ,Anti-P0, anti-ribosomal P0 antibody, C3complement component 3; IgG, immunoglobulin G; SLE, systemic lupus erythematosus.
Table 5. Association between PD-1 expression on PC, SM, NSM, DN and N B cell subsets and the clinic-pathological parameters in SLE patients (mean ± SD, %).
Parameters
|
|
Cases
|
PC PD-1+B cells (%)
|
P value
|
SM PD-1+B cells (%)
|
P value
|
NSM PD-1+B cells (%)
|
P value
|
DN PD-1+B cells (%)
|
P value
|
N PD-1+B cells (%)
|
P value
|
Anti-dsDNA
|
+
|
44
|
7.922±1.685
|
0.040
|
10.38±2.195
|
0.010
|
6.976±0.492
|
0.454
|
17.67±1.212
|
0.928
|
7.894±0.600
|
0.160
|
|
-
|
30
|
4.873±0.373
|
|
5.425±0.372
|
|
6.415±0.540
|
|
17.50±1.495
|
|
6.613±0.647
|
|
Anti-histone
|
+
|
26
|
7.800±1.928
|
0.09
|
9.113±2.459
|
0.196
|
7.000±0.743
|
0.615
|
18.98±1.711
|
0.280
|
7.521±0.726
|
0.812
|
|
-
|
48
|
5.193±0.404
|
|
6.526±0.6131
|
|
6.612±0.397
|
|
16.85±1.103
|
|
7.296±0.569
|
|
Anti-smD1
|
+
|
45
|
6.369±0.867
|
0.661
|
7.029±1.130
|
0.599
|
7.155±0.502
|
0.166
|
17.03±1.041
|
0.450
|
7.376±0.514
|
0.997
|
|
-
|
29
|
5.705±1.314
|
|
8.065±1.699
|
|
6.117±0.495
|
|
18.49±1.768
|
|
7.372±0.824
|
|
Anti-U1snRNP
|
+
|
35
|
6.227±1.105
|
0.880
|
7.640±1.509
|
0.840
|
7.047±0.595
|
0.441
|
16.74±1.427
|
0.389
|
7.548±0.672
|
0.715
|
|
-
|
39
|
6.003±0.988
|
|
7.251±1.212
|
|
6.480±0.442
|
|
18.37±1.234
|
|
7.219±0.600
|
|
Anti-nucleo
|
+
|
35
|
6.397±1.044
|
0.705
|
7.435±1.397
|
1.000
|
6.978±0.598
|
0.544
|
17.75±1.352
|
0.875
|
6.600±0.567
|
0.091
|
|
-
|
39
|
5.836±1.039
|
|
7.435±1.315
|
|
6.531±0.432
|
|
17.45±1.311
|
|
8.108±0.668
|
|
Anti-SSA60
|
+
|
41
|
6.807±1.100
|
0.198
|
7.970±1.444
|
0.449
|
6.646±0.4523
|
0.707
|
18.08±1.197
|
0.489
|
7.022±0.542
|
0.287
|
|
-
|
33
|
4.820±0.397
|
|
6.448±0.4802
|
|
6.936±0.6262
|
|
16.71±1.496
|
|
8.025±0.779
|
|
Anti-SSA52
|
+
|
20
|
8.752±2.518
|
0.027
|
10.19±3.281
|
0.077
|
6.683±0.7926
|
0.914
|
17.75±1.722
|
0.923
|
7.690±0.908
|
0.671
|
|
-
|
54
|
5.130±0.323
|
|
6.413±0.4535
|
|
6.773±0.4091
|
|
17.54±1.121
|
|
7.258±0.514
|
|
Anti-SSB
|
+
|
15
|
8.457±2.422
|
0.107
|
9.016±3.275
|
0.406
|
7.133±0.9511
|
0.598
|
19.14±1.641
|
0.411
|
6.294±0.615
|
0.225
|
|
-
|
59
|
5.512±0.676
|
|
7.033±0.8705
|
|
6.650±0.3917
|
|
17.21±1.096
|
|
7.649±0.533
|
|
Anti-P0
|
+
|
30
|
5.945±0.458
|
0.855
|
7.599±0.8584
|
0.888
|
7.460±0.6516
|
0.107
|
17.19±1.591
|
0.720
|
7.299±0.604
|
0.890
|
|
-
|
44
|
6.220±1.198
|
|
7.323±1.498
|
|
6.263±0.4132
|
|
17.88±1.152
|
|
7.426±0.632
|
|
C3↓
|
Yes
|
58
|
1.256±0.910
|
0.417
|
7.486±1.172
|
0.920
|
6.684±0.4223
|
0.739
|
17.46±1.061
|
0.787
|
7.234±0.485
|
0.551
|
|
No
|
16
|
4.967±0.747
|
|
7.251±1.197
|
|
6.981±0.7278
|
|
18.09±2.037
|
|
7.886±1.098
|
|
IgG↑
|
Yes
|
44
|
6.414±0.890
|
0.627
|
7.700±1.219
|
0.745
|
6.666±0.497
|
0.793
|
16.81±1.316
|
0.323
|
6.909±0.483
|
0.221
|
|
No
|
30
|
5.686±1.252
|
|
7.067±1.538
|
|
6.862±0.539
|
|
18.70±1.282
|
|
8.021±0.824
|
|
LN
|
Yes
|
36
|
7.557±1.424
|
0.054
|
9.6884±1.861
|
0.020
|
6.394±0.474
|
0.347
|
18.82±1.413
|
0.207
|
8.421±0.795
|
0.021
|
|
No
|
38
|
4.737±0.373
|
|
5.301±0.3515
|
|
7.084±0.550
|
|
16.45±1.223
|
|
6.383±0.378
|
|
Malar rash
|
Yes
|
24
|
7.344±2.100
|
0.246
|
8.811±2.699
|
0.320
|
7.443±0.775
|
0.189
|
15.76±1.686
|
0.174
|
7.200±0.725
|
0.788
|
|
No
|
50
|
5.516±0.409
|
|
6.775±0.5732
|
|
6.415±0.388
|
|
18.48±1.112
|
|
7.459±0.565
|
|
Oral ulcer
|
Yes
|
12
|
7.816±3.071
|
0.309
|
10.04±3.767
|
0.231
|
5.722±0.674
|
0.218
|
20.49±2.405
|
0.176
|
8.323±1.094
|
0.353
|
|
No
|
62
|
5.779±0.653
|
|
6.931±0.879
|
|
6.947±0.412
|
|
17.04±1.007
|
|
7.191±0.489
|
|
Arthritis
|
Yes
|
26
|
6.233±1.449
|
0.902
|
8.494±1.873
|
0.417
|
6.505±0.578
|
0.627
|
16.09±1.732
|
0.238
|
7.188±0.796
|
0.761
|
|
No
|
48
|
6.042±0.824
|
|
6.861±1.066
|
|
6.880±0.470
|
|
18.42±1.090
|
|
7.476±0.541
|
|
Serositis
|
Yes
|
18
|
4.698±0.675
|
0.278
|
6.602±1.173
|
0.623
|
6.905±0.7578
|
0.810
|
19.11±1.780
|
0.363
|
6.546±0.729
|
0.296
|
|
No
|
56
|
6.562±0.938
|
|
7.703±1.202
|
|
6.698±0.419
|
|
17.11±1.096
|
|
7.641±0.539
|
|
Interstitial lung
|
Yes
|
13
|
4.205±0.726
|
0.233
|
5.163±0.720
|
0.273
|
5.705±0.744
|
0.188
|
19.58±1.891
|
0.331
|
6.752±0.973
|
0.523
|
|
No
|
61
|
6.515±0.868
|
|
7.919±1.136
|
|
6.971±0.409
|
|
17.18±1.059
|
|
7.507±0.501
|
|
Anti-SmD1,Anti-Smith D1,Anti-dsDNA, Anti-double-stranded DNA; Anti-U1snRNP, Anti-U1 small nuclear ribonucleoprotein; Anti- nucleo, Anti-nucleosomes, Anti-SSA, Anti- Sjögren syndrome antigen A; Anti-SSB, Anti-Sjögren syndrome antigen B, Anti-P0, anti-ribosomal P0 antibody, C3, complement component 3; DN, double negative; IgG, immunoglobulin G; LN, lupus nephritis; N, naïve; NSM, non-switched memory; PC, plasmablast cells; SLE, systemic lupus erythematosus; SM, switched memory.