IgA Nephropathy (IgAN）

Panel A Overexpression of human BAFF drives spontaneous development of LN and IgAN. We further generated dual humanized APRIL/BAFF mice. Phenotype validation and drug efficacy evaluation were performed according to the study design.

Panel B Double knock-in of human BAFF and APRIL elevates serum IgA and anti-dsDNA IgG levels, while Telitacicept treatment reduces serum antibody levels in B6‑hBAFF/hAPRIL mice.

Panel C Increased proteinuria was observed in B6‑hBAFF and B6‑hBAFF/hAPRIL mice, and Telitacicept treatment ameliorated the renal phenotype in B6‑hBAFF/hAPRIL mice.

Panel D Pathological analysis revealed an increased kidney disease score and expanded PAS‑positive area in B6‑hBAFF and B6‑hBAFF/hAPRIL mice; Telitacicept treatment significantly reduced these parameters.

Panel E An expanded B cell population was found in B6‑hBAFF and B6‑hBAFF/hAPRIL mice, and Telitacicept treatment decreased the plasma B cell population in B6‑hBAFF/hAPRIL mice.

Statistical analysis was performed using one‑way ANOVA, and all data are presented as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001,****p<0.0001. 

Panel A Human IgA1 and its receptor, human CD89, were expressed in B6 mice, with CD89 expressed in macrophages under the control of the Cd14 promoter. This double-humanized mouse spontaneously develops an IgAN phenotype. The efficacy of telitacicept was evaluated in this strain. Mice were grouped at 10 weeks of age based on serum human IgA levels (A).

Panel B-C Telitacicept treatment reduced serum human IgA levels and renal IgA deposition at 10 weeks post-treatment.

Statistical analysis was performed using one‑way ANOVA, and all data are presented as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001,****p<0.0001.

Panel A study design establishing the BSA+CCL₄+LPS-induced IgAN mouse model.

Panel B shows serum IgA levels rose gradually with prolonged modeling duration in the model group.

Panel C displays elevated IgA deposition in renal tissues at the experimental endpoint.

Panel D presents typical renal pathological alterations. The model group exhibited a markedly increased renal Kataguchi score. Key pathological lesions are marked as follows: glomerular basement membrane thickening (gray arrow), mesangial cell proliferation (red arrow), mesangial matrix accumulation (green arrow), glomerular fibrinoid necrosis (orange arrow), necrotic cellular debris (black arrow), crescent formation (brown arrow), lymphocyte infiltration (blue arrow), and fibrous tissue hyperplasia (light green arrow).

Panel E reveals enhanced PAS-positive staining in the model group, with glomerular positive signals marked by yellow arrows.

Panel F confirms positive staining of C3, MBL and C1q in renal tissues of the model group.

Statistical analysis was performed using one‑way ANOVA, and all data are presented as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001，****p<0.0001.

Panel A The overall design of the efficacy evaluation study is displayed here.

Panel B LNP023, atrasentan, and its analogue reduced the UTP/CREA ratio 3 weeks post administration.

Panel C Atrasentan analogue lowered serum IgA levels at 4 weeks after administration.

Panel D The model group exhibited decreased RBC, HGB and HCT, indicating the occurrence of renal anemia. Treatment with LNP023 restored these indicators toward normal levels.

Statistical analysis was performed using one‑way ANOVA, and all data are presented as mean ± SEM. *p<0.05, **p<0.01, ***p<0.001，****p<0.0001