Serum IFN-γ Predicts the Therapeutic Effect of Belimumab in Refractory Lupus Nephritis Patients.

IF 1.8 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics & Personalized Medicine Pub Date : 2024-09-30 eCollection Date: 2024-01-01 DOI:10.2147/PGPM.S476308
Shanshan Liu, Ju Li, Zhongyuan Zhang, Deqian Meng, Kai Wang
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Abstract

Objective: To evaluate belimumabf's efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response.

Methods: 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.

Results: 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).

Conclusion: 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.

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血清 IFN-γ 预测贝利木单抗对难治性狼疮肾炎患者的疗效
目的评估贝利木单抗对难治性狼疮肾炎(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患者在基线和开始使用贝利木单抗6个月后的临床反应。采用多重磁珠流式免疫分析法对治疗前后的血清细胞因子(IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ)进行定量分析:14名不同亚型的难治性LN患者参加了研究:7名III级和V级LN患者,3名仅为V级患者,2名III级患者,2名IV+V级和V级LN患者。接受贝利木单抗治疗6个月后,所有参与者的系统性红斑狼疮疾病活动指数(SLEDAI)-2K评分都比各自的基线值有所下降。值得注意的是,大多数患者的泼尼松用量、24 小时尿蛋白水平、免疫球蛋白、红细胞沉降率(ESR)、抗双链 DNA 抗体 IgM 以及血清中 IL-4、IL-6、IL-10 和 IFN-γ 的水平都有所下降。同时,还观察到 C3、C4、IL-2 和 TNF-α 的水平有所上升。参与者中,9 人(64.29%)获得了完全肾脏反应,1 人(7.14%)获得了部分反应,4 人(28.57%)无反应。值得注意的是,与获得完全肾脏反应 (CR) 的患者相比,未获得完全肾脏反应 (CR) 的患者血清 IFN-γ 基线水平更高(p = 0.009)。接收者操作特征(ROC)曲线分析表明,基线IFN-γ水平的曲线下面积(AUC)为0.96(0.70-1.00),灵敏度为0.89,特异性为1.00(p < 0.001):结论:贝利木单抗对治疗难治性LN具有潜在疗效。结论:贝利姆单抗对治疗难治性LN具有潜在疗效。血清IFN-γ基线水平可预测对贝利姆单抗治疗的反应,从而有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。
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来源期刊
Pharmacogenomics & Personalized Medicine
Pharmacogenomics & Personalized Medicine Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
3.30
自引率
5.30%
发文量
110
审稿时长
16 weeks
期刊介绍: Pharmacogenomics and Personalized Medicine is an international, peer-reviewed, open-access journal characterizing the influence of genotype on pharmacology leading to the development of personalized treatment programs and individualized drug selection for improved safety, efficacy and sustainability. In particular, emphasis will be given to: Genomic and proteomic profiling Genetics and drug metabolism Targeted drug identification and discovery Optimizing drug selection & dosage based on patient''s genetic profile Drug related morbidity & mortality intervention Advanced disease screening and targeted therapeutic intervention Genetic based vaccine development Patient satisfaction and preference Health economic evaluations Practical and organizational issues in the development and implementation of personalized medicine programs.
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