Liu Shanshan, Li Ju, Zhang Zhongyuan, Meng Deqian, Wang Kai
Department of Rheumatology and Immunology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, 223001, People's Republic of China.
Pharmgenomics Pers Med. 2024 Sep 30;17:443-452. doi: 10.2147/PGPM.S476308. eCollection 2024.
To evaluate belimumabf's efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response.
In this single-arm retrospective study, we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment.
Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70-1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001).
Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.
评估贝利尤单抗治疗难治性狼疮性肾炎（LN）患者的疗效，并确定治疗反应的预测性血清生物标志物。
在这项单臂回顾性研究中，我们评估了LN患者在基线时以及开始使用贝利尤单抗治疗六个月后的临床反应。在治疗前后，使用多重磁珠流式免疫分析法对血清细胞因子（白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-10、肿瘤坏死因子-α、干扰素-γ）进行定量分析。
14例不同亚型的难治性LN患者参与了本研究：7例为III类和V类LN，3例仅为V类，2例为III类，2例为IV+V类和V类LN。在接受贝利尤单抗治疗六个月后，所有参与者的系统性红斑狼疮疾病活动指数（SLEDAI）-2K评分均较各自的基线值有所降低。值得注意的是，大多数患者的泼尼松剂量、24小时尿蛋白水平、免疫球蛋白、红细胞沉降率（ESR）以及抗双链DNA抗体IgM水平均有所下降，同时血清白细胞介素-4、白细胞介素-6、白细胞介素-10和干扰素-γ水平也有所下降。与此同时，观察到补体C3、C4、白细胞介素-2和肿瘤坏死因子-α水平升高。在参与者中，9例（64.29%）实现了完全肾脏反应，1例（7.14%）表现为部分反应，4例（28.57%）无反应。值得注意的是，与实现完全肾脏反应（CR）的患者相比，未实现完全肾脏反应的患者基线血清干扰素-γ水平更高（p = 0.009）。受试者工作特征（ROC）曲线分析表明，基线干扰素-γ水平的曲线下面积（AUC）为0.96（0.70-1.00），敏感性为0.89，特异性为1.00（p < 0.001）。
贝利尤单抗在治疗难治性LN方面显示出潜在疗效。基线血清干扰素-γ水平可能预测对贝利尤单抗治疗的反应，这可能为这种具有挑战性的疾病提供更具针对性的治疗方法。
