Sidner Richard A, Book Benita K, Agarwal Avinash, Bearden Christopher M, Vieira Carlos A, Pescovitz Mark D
Indiana University School of Medicine, Department of Surgery, Indianapolis, IN 46202, USA.
Hum Antibodies. 2004;13(3):55-62.
Rituximab, chimeric anti-human CD20 monoclonal antibody approved for B-cell lymphoma, depletes circulating B cells. Little data exist on its use for nonmalignant diseases or B-cell subset recovery after treatment. We hypothesized that rituximab may reduce panel reactive alloantibodies (PRA) in dialysis patients awaiting renal transplantation and performed a single-dose, dose-escalation phase 1 trial. Here we report changes in lymphocyte phenotypes in subjects treated with rituximab alone. Nine subjects, 44 +/- 10 years(Yr); (5 F, 4 M) received one dose (n=3) at 50, 150, or 375 mg/m(2) without other immunosuppression. Blood was collected before dosing and intervals thereafter. No significant changes in leukocytes, total or CD3(+) lymphocytes were noted. In all, there was CD19(+) depletion by day 2(D2) (12.0 +/- 5.6 cells/mm(3) vs. 181 +/- 137, D0; p<0.01) and CD20(+) (11.0 +/- 12.0 vs. 205 +/- 116, D0; p<0.01). At 6 months (mo), CD19(+) and CD20(+) remained low (51.1 +/- 42.2, p<0.05; 75.4 +/- 38.7, p<0.05, respectively) compared to D0. CD19(+)CD5(+) cells recovered more rapidly, returning to baseline by 6mo while B memory cells (CD19(+)CD27(+)) remained low (32.3 +/- 29.0) at 1Yr (7.5 +/- 4.5; p<0.001) and 2Yr (12.1 +/- 7.9; p<0.001) after treatment. We conclude that single dose rituximab ablates B cells in high PRA dialysis patients awaiting transplantation. B-cell ablation, particularly memory B cells, was long-lasting, lagging repopulation by CD5(+) B cells.
利妥昔单抗是一种被批准用于治疗B细胞淋巴瘤的嵌合抗人CD20单克隆抗体，可消耗循环中的B细胞。关于其在非恶性疾病中的应用或治疗后B细胞亚群恢复的数据很少。我们推测利妥昔单抗可能会降低等待肾移植的透析患者的群体反应性同种抗体（PRA），并进行了一项单剂量、剂量递增的1期试验。在此，我们报告单独接受利妥昔单抗治疗的受试者淋巴细胞表型的变化。9名受试者，年龄44±10岁（岁）；（5名女性，4名男性）在未使用其他免疫抑制剂的情况下，分别接受了50、150或375mg/m²的一剂治疗（n = 3）。在给药前及之后的不同时间点采集血液。白细胞、总淋巴细胞或CD3⁺淋巴细胞未见显著变化。总体而言，到第2天（D2）时CD19⁺细胞减少（12.0±5.6个细胞/mm³ 对比 D0时的181±137个细胞/mm³；p<0.01），CD20⁺细胞也减少（11.0±12.0对比D0时的205±116；p<0.01）。在6个月（mo）时，与D0相比，CD19⁺和CD20⁺细胞数量仍然较低（分别为51.1±42.2，p<0.05；75.4±38.7，p<0.05）。CD19⁺CD5⁺细胞恢复得更快，在6个月时恢复到基线水平，而B记忆细胞（CD19⁺CD27⁺）在治疗后1年（7.5±4.5；p<0.001）和2年（12.1±7.9；p<0.001）时仍然较低（32.3±29.0）。我们得出结论，单剂量利妥昔单抗可消除等待移植且PRA较高的透析患者的B细胞。B细胞清除，尤其是记忆B细胞，持续时间较长，CD5⁺B细胞的再填充滞后。
