Bearden Christopher M, Agarwal Avinash, Book Benita K, Vieira Carlos A, Sidner Richard A, Ochs Hans D, Young Marquerite, Pescovitz Mark D
Department of Surgery, Indiana University, Indianapolis, IN, USA.
Am J Transplant. 2005 Jan;5(1):50-7. doi: 10.1111/j.1600-6143.2003.00646.x.
The response to primary immunization in patients treated with Rituximab (RIT) is not clear. We studied the in vivo antibody response of chronic renal failure (CRF) patients to the neoantigen bacteriophage phiX174 given alone or after ablation with RIT. Eighteen CRF subjects received two immunizations with phiX174 separated by 6 weeks. Nine subjects received a single dose of RIT. The intensity and immunoglobulin isotype of the antibody response (K(v)) were measured post-infusion. In addition, three subjects previously immunized and treated with RIT underwent a third and fourth immunization with phiX174 and a tetanus control 2 years later. RIT significantly decreased peak K(v) responses when compared to both historic non-CRF controls and to CRF subjects. CRF itself decreased peak K(v) responses compared to non-CRF controls. Percent-ratio of anti-phage IgM to IgG was significantly decreased in RIT treated subjects. One of three subjects treated with RIT was found to have developed a partial B cell tolerance to phiX174 administration 2 years later. RIT decreases antibody production and isotype switching to neoantigens and might be useful to prevent antibody response to therapeutic drugs and to newly transplanted organs.
利妥昔单抗(RIT)治疗患者对初次免疫的反应尚不清楚。我们研究了慢性肾衰竭(CRF)患者对单独给予或在用RIT清除后给予的新抗原噬菌体φX174的体内抗体反应。18名CRF受试者接受了两次间隔6周的φX174免疫接种。9名受试者接受了单剂量的RIT。在输注后测量抗体反应(K(v))的强度和免疫球蛋白同种型。此外,3名先前接受过免疫接种并接受RIT治疗的受试者在2年后接受了第三次和第四次φX174免疫接种以及破伤风对照。与历史非CRF对照和CRF受试者相比,RIT显著降低了峰值K(v)反应。与非CRF对照相比,CRF本身降低了峰值K(v)反应。在接受RIT治疗的受试者中,抗噬菌体IgM与IgG的百分比显著降低。发现接受RIT治疗的3名受试者中有1名在2年后对φX174给药产生了部分B细胞耐受性。RIT可降低抗体产生和对新抗原的同种型转换,可能有助于预防对治疗药物和新移植器官的抗体反应。