Pre-existing anti-HLA allo-antibodies (allo-Abs) are a major barrier to successful kidney transplantation, resulting in an elevated risk for antibody-mediated rejection (AMR) and eventual graft loss. The cytokine B lymphocyte stimulator (BLyS) promotes B cell maturation and plasma cell survival; consequently, anti-BLyS therapy represents a potential therapeutic opportunity in diminishing pre-existing allo-Abs. Here we report that in our 1-year pilot trial, BLyS neutralization failed to reduce total anti-HLA allo-Ab levels in highly sensitized candidates awaiting kidney transplant in a clinically meaningful way. Additionally, we performed a post hoc analysis using sera from trial candidates which revealed selective depletion of anti-HLA class I and class II Abs in response to belimumab treatment, restricted to certain allele specificities and IgG subclasses. Altogether, we observed that BLyS blockade only results in selective depletion of anti-HLA Abs recognizing a few discrete HLA allele specificities.

预先存在的抗 HLA 同种抗体 (allo-Abs) 是成功进行肾移植的主要障碍，导致抗体介导排斥 (AMR) 和最终移植物丢失的风险升高。细胞因子 B 淋巴细胞刺激物 (BLyS) 促进 B 细胞成熟和浆细胞存活；因此，抗BLyS疗法代表了减少预先存在的allo-Abs的潜在治疗机会。在这里，我们报告说，在我们为期 1 年的试点试验中，BLyS 中和未能以具有临床意义的方式降低等待肾移植的高度致敏候选者的总抗 HLA 同种异体抗体水平。此外，我们进行了事后使用来自试验候选者的血清进行分析，结果显示抗 HLA I 类和 II 类抗体对贝利木单抗治疗的选择性消耗，仅限于某些等位基因特异性和 IgG 亚类。总之，我们观察到 BLyS 阻断仅导致选择性耗尽抗 HLA Abs，识别一些离散的 HLA 等位基因特异性。