Introduction
Materials and methods
Patients and vaccination
Parameter | Post-rituximab (n = 11) | Pre-rituximab (n = 8) | Controls (n = 10) |
---|---|---|---|
Vaccination time | 6 months after RTX | 6 days before RTX | No RTX |
B cells (% of mononuclear cells in circulation) (mean ± SD) | 2.2 ± 5.2 | 4.7 ± 4.1 | 6.1 ± 2.9 |
Age, years (mean ± SD, range) | 60.4 ± 7.8 (45-70) | 65.4 ± 11.5 (55-82) | 63.6 ± 12.9 (48-95) |
Gender, m/f | 1/10 | 1/7 | 3/7 |
Disease duration, years (range) | 17.3 ± 13.1 (6-33) | 8.6 ± 5.5 (3-18) | 7.4 ± 4.6 (2-16) |
Erosive | 10 (91%) | 7 (87%) | 9 (90%) |
RF, positive | 11 | 8 | 10 |
Treatment | |||
MTX, n (mg/week, mean ± SD) | 10 (17.7 ± 6.3)a | 7 (18.7 ± 5.4)b | 10 (18.3 ± 5.6) |
Previous anti-TNF, n | 10 | 5 | 2 |
Previous RTX, n | 4 | 1 | 0 |
Time after previous RTX, months | 30 months (14-48) | 24 months | 0 |
Patients | Prednisolone (mg/day) | MTX (mg/week) | Other |
---|---|---|---|
Pre-RTX | |||
1 | 0 | 12.5 | |
2 | 5 | 25 | |
3 | 7.5 | 20 | |
4 | 6.25 | 10 | |
5 | 10 | 20 | |
Post-RTX | |||
1 | 5 | 20 | |
2 | 0 | 20 | Cyclosporin A |
3 | 0 | 25 | |
4 | 0 | 15 | |
5 | 5 | 10 | |
6 | 5 | 25 | |
7 | 0 | 2.5 | Azathioprine |
8 | 0 | 10 | |
9 | 2.5 | 22.5 | Cyclosporin A |
10 | 0 | 20 | |
11 | 5 | 10 | |
Controls | |||
1 | 0 | 15 | Sulfasalazine |
2 | 5 | 10 | |
3 | 0 | 25 | Sulfasalazine |
4 | 0 | 10 | Hydroxychlorokin + cyclosporin A |
5 | 0 | 20 | Hydroxychlorokin |
6 | 0 | 20 | Etanercept |
7 | 0 | 20 | |
8 | 0 | 25 | Hydroxychlorokin |
9 | 0 | 20 | Infliximab |
10 | 0 | 20 |
Controls n = 10 | Pre-RTX n = 8 | Post-RTX n = 11 | |
---|---|---|---|
Influenza vaccine, % increase | |||
IgM, median (95% CI) responder, n | 104 (96-130) 3 | 120 (98-139) 6 | 105 (88-132) 4 |
IgG, median (95% CI) responder, n | 115 (96-191) 6 | 143 (72-176) 5 | 109 (85-139)a 5 |
κ-Light chain median (95% CI) | 110 (101-145)a | 126 (98-163) | 105 (93-124) |
λ-Light chain median (95% CI) | 126 (98-175)a | 147 (94-154)a | 113 (93-199)a |
Pneumococci vaccine | |||
IgM, median (95% CI) responder, n | 148 (92-541)a 8 | 107 (93-198) 3 | 105 (77-322) 5 |
IgG, median (95% CI) responder, n | 126 (71-213)a 7 | 178 (102-335)a 6 | 107 (88-151)b 4 |
κ-Light chain median (95% CI) | 154 (85/218)a | 124 (97-211)a | 105 (94-171) |
λ-Light chain median (95% CI) | 164 (98/571)a | 227 (111-308)a | 138 (88-330)a |
Detection of vaccine-specific antibody production
Statistical analyses
Results
Evaluation of B-cell numbers in the study groups
Vaccine-specific cellular responses after RTX treatment
Vaccine-specific humoral responses after RTX treatment
IgG isotypes of vaccine-specific response to influenza and Pneumo23
Patients | Total IgG | IgG1 | IgG2 | IgG3 | IgG4 | Total IgG | IgG1 | IgG2 | IgG3 | IgG4 | Previous RTX |
---|---|---|---|---|---|---|---|---|---|---|---|
Influenza | P23 | ||||||||||
Pre-RTX | |||||||||||
1 |
176
|
289
| 99 |
125
|
117
|
152
| 95 | 105 |
110
|
115
| 1 |
2 a | 94 | 86 | 98 | 89 | 74 |
102
|
454
|
534
|
203
|
117
| no |
3 a |
163
|
128
|
110
|
112
|
111
|
204
|
262
| 107 | 95 |
115
| no |
4 a |
154
|
292
|
198
|
178
|
108
|
335
| 77 |
167
|
129
|
148
| no |
5 a |
132
|
368
| 99 |
121
|
123
|
217
|
246
|
458
|
128
|
113
| no |
Post-RTX | |||||||||||
1a |
139
|
202
|
123
|
116
|
153
|
151
| 83 | 85 | 95 | 102 | no |
2 |
126
|
260
|
133
|
136
|
158
|
110
| 103 | 104 | 95 | 101 | 2 |
3 | 109 | 93 |
115
|
110
|
107
| 107 |
143
| 105 | 107 |
116
| no |
4 | 100 | 97 | 89 | 102 | 91 | 102 | 104 | 98 |
111
|
112
| no |
5a |
115
| 89 | 72 | 100 | 96 | 93 | 87 |
211
|
112
| 108 | no |
6a | 85 | 93 | 76 | 87 | 102 | 88 | 82 |
187
| 96 | 107 | 3 |
7 | 98 | 82 | 94 | 96 | 97 | 107 | 95 | 94 | 98 | 94 | no |
8 | 103 | 99 | 86 |
124
|
113
| 95 |
233
|
257
|
126
|
117
| no |
9a | 104 | 102 |
115
| 91 | 103 |
126
| 92 | 105 | 92 | 98 | 1 |
10 |
127
|
222
|
115
|
160
|
170
| 104 |
159
|
248
|
175
|
206
| 2 |
11a |
134
|
157
|
110
|
119
|
109
|
122
|
167
|
140
|
125
|
144
| no |
Controls | |||||||||||
1 |
117
| 95 | 84 |
113
| 108 |
213
| 91 |
171
| 89 | 83 | no |
2a |
191
|
252
| 96 |
125
|
127
|
115
|
897
|
521
|
235
|
278
| no |
3 | 100 |
157
| 100 | 50 | 105 |
139
| 137 |
178
| 109 | 95 | no |
4 | 96 |
145
| 97 | 105 |
113
|
136
| 467 |
216
|
159
|
137
| no |
5 |
121
|
205
| 101 |
191
|
126
| 105 |
114
|
112
| 107 |
111
| no |
6 |
116
|
124
|
123
| 108 |
119
| 97 |
154
|
136
|
151
|
112
| no |
7 |
113
|
123
|
179
|
111
|
111
| 71 |
316
|
259
|
120
|
122
| no |
8 |
174
|
234
|
127
|
146
|
121
|
161
|
167
|
140
| 108 | 105 | no |
9 | 97 | 98 | 72 |
144
|
123
|
111
| 65 | 84 |
114
| 101 | no |
10 | 99 |
142
|
116
|
129
|
124
|
194
|
271
|
122
|
132
|
889
| no |