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 China

Correspondence: 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 morrosun@hotmail.com

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.

Keywords: refractory lupus nephritis, belimumab, treatment, biomarker, IFN-γ