Pharmacogenomics and Personalized Medicine (Sep 2024)
Serum IFN-γ Predicts the Therapeutic Effect of Belimumab in Refractory Lupus Nephritis Patients
Abstract
Shanshan Liu, Ju Li, Zhongyuan Zhang, Deqian Meng, Kai Wang Department of Rheumatology and Immunology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, 223001, People’s Republic of ChinaCorrespondence: Kai Wang, Department of Rheumatology and Immunology, The affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, 223001, People’s Republic of China, Tel/Fax +86-17551710317, Email [email protected]: 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.Keywords: refractory lupus nephritis, belimumab, treatment, biomarker, IFN-γ
