Jaffers G J, Fuller T C, Cosimi A B, Russell P S, Winn H J, Colvin R B
Transplantation. 1986 May;41(5):572-8. doi: 10.1097/00007890-198605000-00004.
The frequency, timing, and specificity of the humoral antibody response to a murine monoclonal antibody (OKT3, IgG2a) were measured in 21 consecutive renal allograft recipients. These patients received i.v. OKT3, 1-5 mg/day for 10-20 days as treatment for acute graft rejection. Maintenance immunosuppression consisted of azathioprine and corticosteroids. Using three different assays, an antibody response was detected in 75% of the 20 patients with adequate samples. The ELISA assay of the overall IgM and IgG reactivity to OKT3 revealed that IgM anti-OKT3 appeared in 65% and IgG anti-OKT3 in 50% of the patients, reaching a peak 20-33 days after the last dose of OKT3. The IgM preceeded the IgG in most cases (P less than 0.02) and in 8 cases was detected during therapy. One patient had high levels of IgM anti-OKT3 before therapy, yet responded normally to OKT3. Interference with the therapeutic effectiveness was evident in one patient who developed IgG antibodies during therapy. His serum blocked the binding of F-OKT3 to normal lymphocytes in the presence of normal BALB/c serum. The blocking assay, done by flow cytometry, measured anti-idiotypic (Id) reactivity since the sera did not affect the binding of OKT8 (another IgG2a) or anti-Leu4 (another anti-T3), and the blocking activity remained after affinity absorption with normal mouse IgG. Using this assay, 60% of the patients made an anti-Id response. One made only anti-Id, and several had anti-Id at times when other reactivities were undetectable. Antibodies to non-idiotypic, presumably isotypic, determinants represented on OKT8 occurred in only 44%, while other reactivity (OKT4; IgG2bK) was less common (12%) and weaker. While no adverse allergic reactions occurred in this group of patients, the anti-Id antibodies, which are a prominent feature of the immune response to this and probably other monoclonal antibodies, can block their therapeutic effectiveness and can arise despite intense immunosuppression. This response may require the use of different idiotypes for prolonged or repeated courses of therapy and may be the major obstacle to the use of human monoclonal antibodies.
在21例连续的肾移植受者中，检测了对鼠单克隆抗体（OKT3，IgG2a）的体液抗体反应的频率、时间和特异性。这些患者静脉注射OKT3，1 - 5毫克/天，持续10 - 20天，作为急性移植排斥反应的治疗。维持免疫抑制包括硫唑嘌呤和皮质类固醇。使用三种不同的检测方法，在20例有足够样本的患者中，75%检测到抗体反应。对OKT3的总体IgM和IgG反应性的ELISA检测显示，65%的患者出现IgM抗OKT3，50%的患者出现IgG抗OKT3，在最后一剂OKT3后20 - 33天达到峰值。在大多数情况下（P小于0.02），IgM先于IgG出现，8例在治疗期间检测到。1例患者在治疗前IgM抗OKT3水平较高，但对OKT3反应正常。1例患者在治疗期间产生IgG抗体，其血清在正常BALB/c血清存在下阻断F - OKT3与正常淋巴细胞的结合，这明显干扰了治疗效果。通过流式细胞术进行的阻断检测测量了抗独特型（Id）反应性，因为血清不影响OKT8（另一种IgG2a）或抗Leu4（另一种抗T3）的结合，并且在用正常小鼠IgG进行亲和吸收后阻断活性仍然存在。使用这种检测方法，60%的患者产生了抗Id反应。1例仅产生抗Id，有几例在其他反应性无法检测到时出现抗Id。针对OKT8上非独特型、推测为同种型决定簇的抗体仅在44%的患者中出现，而其他反应性（OKT4；IgG2bK）较少见（12%）且较弱。虽然该组患者未发生不良过敏反应，但抗Id抗体是对这种以及可能其他单克隆抗体免疫反应的一个突出特征，它可阻断其治疗效果，并且尽管有强烈的免疫抑制仍可能出现。对于延长或重复疗程的治疗，可能需要使用不同的独特型，这可能是使用人单克隆抗体的主要障碍。
