Roll Petra, Mahmood Zafar, Muhammad Khalid, Feuchtenberger Martin, Dörner Thomas, Tony Hans-Peter
Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
Charité, Universitätsmedizin Berlin and DRFZ Berlin, Germany.
Clin Exp Rheumatol. 2015 May-Jun;33(3):347-53. Epub 2015 Apr 16.
B-cell depletion using rituximab (RTX) has proven efficacy in patients with RA. Long-term effects on the B-cell system after single and repeated treatments are sparse. Our aim was to study the effect of multiple courses of rituximab to evaluate its impact on repeated B-cell re-population capacity.
Two cohorts, altogether 20 patients with RA were included in an open label extension study with RTX. Cohort 1 received one cycle RTX and was followed for up to 7 years. In cohort 2 patients were studied under up to 5 cycles of RTX. Immunophenotyping was performed before therapy and during follow-up.
After a single therapy with RTX (cohort 1) the frequency of pre-switch (MZ-like) B cells were significantly reduced during the follow-up of 7 years and absolute numbers slowly repopulated to nearly 50% of baseline value without numerical normalisation. The acquisition of mutations in Ig receptors of pre-switch (MZ-like) memory B cells was also significantly reduced 10 years after one course. In contrast, absolute numbers of (classical) post-switch B cells tended to normalise to baseline values after 7 years. Analysing B-cell repopulation capacities after multiple cycles revealed (cohort 2) a comparable repopulation pattern after each cycle with no substantial further impact on memory B cells.
A single therapy with RTX leads to long-term changes in the memory B-cell compartment particularly in pre-switch memory B cells. Multiple cycles of RTX show a comparable repopulation pattern after each cycle with no additional cumulative effect on memory B cells.
已证实使用利妥昔单抗（RTX）清除B细胞对类风湿关节炎（RA）患者有效。单次和重复治疗后对B细胞系统的长期影响数据较少。我们的目的是研究多疗程利妥昔单抗的效果，以评估其对B细胞重复再填充能力的影响。
两个队列共20例RA患者纳入了一项使用RTX的开放标签扩展研究。队列1接受一个周期的RTX治疗，并随访长达7年。队列2的患者接受多达5个周期的RTX治疗。在治疗前和随访期间进行免疫表型分析。
在队列1单次使用RTX治疗后，在7年的随访期间，转换前（MZ样）B细胞的频率显著降低，其绝对数量缓慢重新填充至基线值的近50%，但未恢复至正常数值。一个疗程后10年，转换前（MZ样）记忆B细胞Ig受体突变的发生率也显著降低。相比之下，（经典的）转换后B细胞的绝对数量在7年后趋于恢复至基线值。分析多周期后的B细胞再填充能力（队列2）显示，每个周期后的再填充模式相似，对记忆B细胞没有实质性的进一步影响。
单次使用RTX治疗会导致记忆B细胞区室发生长期变化，尤其是转换前记忆B细胞。多周期的RTX治疗在每个周期后显示出相似再填充模式，对记忆B细胞没有额外的累积影响。
