Department of Medicine and.
Blood. 2013 Sep 12;122(11):1946-53. doi: 10.1182/blood-2013-04-494096. Epub 2013 Jul 12.
B-cell depletion may impair vaccine responses and increase infection risk in patients with immune thrombocytopenia (ITP). We investigated the effects of rituximab on antibody and cellular responses to Streptococcus pneumoniae polysaccharide and Haemophilus influenzae type b (Hib) vaccines in ITP patients. Of 60 patients in the main trial, 24 patients received both vaccines 6 months after rituximab (n = 17) or placebo (n = 7). Among 20 evaluable patients, 3 of 14 (21%) in the rituximab group and 4 of 6 (67%) in the placebo group achieved a fourfold increase in anti-pneumococcal antibodies (P = .12). For anti-Hib antibodies, 4 of 14 (29%) and 5 of 6 (83%), respectively, achieved a fourfold increase (P < .05). Fewer patients in the rituximab group demonstrated Hib killing (2 of 14 [14%], 5 of 6 [83%], P < .05). Three of 14 rituximab-treated patients failed to respond to vaccines by any criteria. After vaccinations, preplasma cell blasts and interferon-γ-secreting T cells were reduced in rituximab-treated patients. Antibody responses were impaired for at least 6 months after rituximab. Cellular immunity was reduced in parallel with depleted B-cell pools. These findings have implications for the timing of vaccinations and the mechanism of infection after rituximab in ITP patients.
B 细胞耗竭可能会损害免疫性血小板减少症 (ITP) 患者对疫苗的反应并增加感染风险。我们研究了利妥昔单抗对 ITP 患者对肺炎球菌多糖和流感嗜血杆菌 b 型 (Hib) 疫苗的抗体和细胞反应的影响。在主要试验的 60 名患者中，有 24 名患者在利妥昔单抗（n = 17）或安慰剂（n = 7）治疗 6 个月后接种了这两种疫苗。在 20 名可评估的患者中，利妥昔单抗组的 14 名患者中有 3 名（21%）和安慰剂组的 6 名患者中有 4 名（67%）的抗肺炎球菌抗体增加了 4 倍（P =.12）。对于抗 Hib 抗体，14 名患者中有 4 名（29%）和 6 名患者中有 5 名（83%）增加了 4 倍（P <.05）。利妥昔单抗组中较少的患者显示 Hib 杀伤（14 名患者中有 2 名 [14%]，6 名患者中有 5 名 [83%]，P <.05）。在任何标准下，14 名利妥昔单抗治疗的患者中有 3 名未能对疫苗产生反应。接种疫苗后，利妥昔单抗治疗的患者前浆母细胞和干扰素-γ分泌 T 细胞减少。抗体反应在利妥昔单抗治疗后至少 6 个月内受到损害。细胞免疫与耗竭的 B 细胞池平行降低。这些发现对 ITP 患者利妥昔单抗治疗后的疫苗接种时间和感染机制有影响。
