Looney Cary M, Strauli Nicolas, Cascino Matthew D, Garma Hailey, Schroeder Aaron V, Takahashi Chikara, O'Gorman William, Green Cherie, Herman Ann E
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Genentech, Inc., South San Francisco, CA, USA.
Clin Immunol. 2023 Mar;248:109265. doi: 10.1016/j.clim.2023.109265. Epub 2023 Feb 14.
Targeted B-cell depletion is a useful therapy for many diseases, including autoimmune disorders and certain cancers. We developed a sensitive blood B-cell depletion assay, MRB 1.1, compared its performance with the T-cell/B-cell/NK-cell (TBNK) assay, and assessed B-cell depletion with different therapies. The empirically defined lower limit of quantification (LLOQ) for CD19+ cells in the TBNK assay was 10 cells/μL, and 0.441 cells/μL for the MRB 1.1 assay. The TBNK LLOQ was used to compare differences between B-cell depletion in similar lupus nephritis patient populations who received rituximab (LUNAR), ocrelizumab (BELONG), or obinutuzumab (NOBILITY). After 4 weeks, 10% of patients treated with rituximab retained detectable B cells vs 1.8% with ocrelizumab and 1.7% for obinutuzumab; at 24 weeks 93% of patients who received obinutuzumab remained below LLOQ vs 63% for rituximab. More-sensitive measurements of B cells may reveal differences in potency among anti-CD20 agents, which may associate with clinical outcomes.
靶向B细胞清除疗法对许多疾病都有效，包括自身免疫性疾病和某些癌症。我们开发了一种灵敏的血液B细胞清除检测方法MRB 1.1，将其性能与T细胞/B细胞/NK细胞（TBNK）检测方法进行比较，并评估不同疗法的B细胞清除效果。TBNK检测中CD19+细胞的经验性定义定量下限（LLOQ）为10个细胞/μL，而MRB 1.1检测为0.441个细胞/μL。TBNK的LLOQ用于比较接受利妥昔单抗（LUNAR）、奥瑞珠单抗（BELONG）或奥妥珠单抗（NOBILITY）治疗的相似狼疮性肾炎患者群体中B细胞清除的差异。4周后，接受利妥昔单抗治疗的患者中有10%仍可检测到B细胞，而接受奥瑞珠单抗治疗的为1.8%，接受奥妥珠单抗治疗的为1.7%；在24周时，接受奥妥珠单抗治疗的患者中有93%仍低于LLOQ，而接受利妥昔单抗治疗的为63%。对B细胞更灵敏的测量可能揭示抗CD20药物之间效力的差异，这可能与临床结果相关。
