Bingham Clifton O, Looney R John, Deodhar Atul, Halsey Neal, Greenwald Maria, Codding Christine, Trzaskoma Benjamin, Martin Flavius, Agarwal Sunil, Kelman Ariella
Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland 21224, USA.
Arthritis Rheum. 2010 Jan;62(1):64-74. doi: 10.1002/art.25034.
To examine immunization responses in patients with rheumatoid arthritis (RA) treated with rituximab and to investigate the effects of rituximab-induced CD20+ B cell depletion on immune responses to tetanus toxoid (T cell-dependent antigen), pneumococcal polysaccharide (T cell-independent antigen), and keyhole limpet hemocyanin (KLH) (neoantigen) and on delayed-type hypersensitivity (DTH).
In a controlled trial, we enrolled 103 patients with active RA receiving a stable dose of methotrexate (MTX). Tetanus toxoid, pneumococcal polysaccharide, and KLH vaccines as well as a Candida albicans skin test were administered to 1 group of patients receiving rituximab plus MTX (called rituximab-treated patients) for 36 weeks and to 1 group of patients receiving MTX alone for 12 weeks. The primary end point was the proportion of patients with a >or=4-fold rise in antitetanus IgG levels. Antitetanus, antipneumococcal, and anti-KLH serum IgG levels were measured prior to and 4 weeks following vaccine administration. The DTH response to C albicans was measured 2-3 days following placement.
Responses to tetanus toxoid vaccine (>or=4-fold rise) were similar in both groups (39.1% of rituximab-treated patients and 42.3% of patients treated with MTX alone). The ability to maintain a positive DTH response to the C albicans skin test was comparable in both groups (77.4% of rituximab-treated patients and 70% of patients treated with MTX alone), showing no effect of rituximab treatment. Rituximab-treated patients had decreased responses to pneumococcal polysaccharide vaccine (57% of patients had a 2-fold rise in titer in response to >or=1 serotype, compared with 82% of patients treated with MTX alone) and to KLH vaccine (47% of patients had detectable anti-KLH IgG, compared with 93% of patients treated with MTX alone).
Recall responses to the T cell-dependent protein antigen tetanus toxoid as well as DTH responses were preserved in rituximab-treated RA patients 24 weeks after treatment. Responses to neoantigen (KLH) and T cell-independent responses to pneumococcal vaccine were decreased, but many patients were able to mount responses. These data suggest that polysaccharide and primary immunizations should be administered prior to rituximab infusions to maximize responses.
研究接受利妥昔单抗治疗的类风湿关节炎（RA）患者的免疫反应，并调查利妥昔单抗诱导的CD20+B细胞耗竭对破伤风类毒素（T细胞依赖性抗原）、肺炎球菌多糖（T细胞非依赖性抗原）和钥孔戚血蓝蛋白（KLH）（新抗原）免疫反应以及对迟发型超敏反应（DTH）的影响。
在一项对照试验中，我们纳入了103例接受稳定剂量甲氨蝶呤（MTX）治疗的活动性RA患者。对一组接受利妥昔单抗加MTX治疗的患者（称为利妥昔单抗治疗组患者）给予破伤风类毒素、肺炎球菌多糖和KLH疫苗以及白色念珠菌皮肤试验，持续36周，对另一组仅接受MTX治疗的患者给予上述处理，持续12周。主要终点是抗破伤风IgG水平升高≥4倍的患者比例。在疫苗接种前和接种后4周测量抗破伤风、抗肺炎球菌和抗KLH血清IgG水平。在接种后2 - 3天测量对白色念珠菌的DTH反应。
两组对破伤风类毒素疫苗的反应（升高≥4倍）相似（利妥昔单抗治疗组患者中39.1%，仅接受MTX治疗的患者中42.
