Department of Surgery, Indiana University, Indianapolis, IN, USA.
J Allergy Clin Immunol. 2011 Dec;128(6):1295-1302.e5. doi: 10.1016/j.jaci.2011.08.008. Epub 2011 Sep 9.
B-lymphocyte depletion with rituximab has been shown to benefit patients with various autoimmune diseases. We have previously demonstrated that this benefit is also apparent in patients with newly diagnosed type 1 diabetes.
The effect of rituximab on in vivo antibody responses, particularly during the period of B-lymphocyte depletion, is incompletely determined. This study was designed to assess this knowledge void.
In patients with recent-onset type 1 diabetes treated with rituximab (n = 46) or placebo (n = 29), antibody responses to neoantigen phiX174 during B-lymphocyte depletion and with hepatitis A (as a second neoantigen) and tetanus/diphtheria (as recall antigens) after B-lymphocyte recovery were studied. Anti- tetanus, diphtheria, mumps, measles, and rubella titers were measured before and after treatment by means of ELISA. Antibody titers and percentage IgM versus percentage IgG to phiX174 were measured by means of phage neutralization. B-lymphocyte subsets were determined by means of flow cytometry.
No change occurred in preexisting antibody titers. Tetanus/diphtheria and hepatitis A immunization responses were protective in the rituximab-treated subjects, although significantly blunted compared with those seen in the controls subjects, when immunized at the time of B-lymphocyte recovery. Anti-phiX174 responses were severely reduced during the period of B-lymphocyte depletion, but with B-lymphocyte recovery, anti-phiX174 responses were within the normal range.
During the time of B-lymphocyte depletion, rituximab recipients had a decreased antibody response to neoantigens and significantly lower titers after recall immunization with diphtheria and tetanus toxoid. With recovery, immune responses return toward normal. Immunization during the time of B-lymphocyte depletion, although ineffective, does not preclude a subsequent response to the antigen.
利妥昔单抗（rituximab）诱导的 B 淋巴细胞耗竭已被证明有益于多种自身免疫性疾病患者。我们之前已经证明，这种益处也出现在新诊断的 1 型糖尿病患者中。
利妥昔单抗对体内抗体反应的影响，特别是在 B 淋巴细胞耗竭期间的影响，尚未完全确定。本研究旨在评估这一知识空白。
在接受利妥昔单抗（n=46）或安慰剂（n=29）治疗的新近诊断为 1 型糖尿病患者中，研究了 B 淋巴细胞耗竭期间对新抗原 phiX174、甲型肝炎（作为第二种新抗原）和破伤风/白喉（作为回忆抗原）的抗体反应。在治疗前后，通过 ELISA 测量抗破伤风、白喉、腮腺炎、麻疹和风疹的滴度。通过噬菌体中和法测量 phiX174 的抗体滴度和 IgM 百分比与 IgG 百分比。通过流式细胞术测定 B 淋巴细胞亚群。
未观察到预先存在的抗体滴度发生变化。在接受利妥昔单抗治疗的患者中，破伤风/白喉和甲型肝炎免疫接种反应是保护性的，尽管与对照组相比，在 B 淋巴细胞恢复时免疫接种时，反应明显减弱。在 B 淋巴细胞耗竭期间，抗 phiX174 反应严重减少，但随着 B 淋巴细胞恢复，抗 phiX174 反应恢复正常范围。
在 B 淋巴细胞耗竭期间，利妥昔单抗治疗组对新抗原的抗体反应降低，破伤风类毒素和白喉类毒素回忆免疫后的抗体滴度显著降低。随着恢复，免疫反应恢复正常。在 B 淋巴细胞耗竭期间进行免疫接种虽然无效，但并不排除对随后抗原的反应。
