Work

Bispecific MASP-2/3 antibody provides superior renoprotection over monotherapy in pristane-induced lupus nephritis

Year: 2026

Type: article

Abstract: Lupus nephritis (LN) is a major cause of organ damage in systemic lupus erythematosus and is driven in part by overactivation of the lectin pathway (LP) and alternative pathway (AP) of complement. Mannan-binding lectin-associated serine protease-2 (MASP-2) initiates LP through C4/C2 cleavage, whereas MASP-3 enables AP amplification by activating pro-factor D. We hypothesized that concurrent inhibition of both proteases would provide superior renoprotection compared with single-pathway blockade in established disease. Female BALB/c mice with pristane-induced LN received anti-MASP-2, anti-MASP-3, bispecific antibodies, or vehicle for 4 weeks. Bispecific MASP-2/3 inhibition produced greater improvements in albuminuria, renal activity index, and glomerular C3d and C5b-9 deposition than either monotherapy. Functional assays confirmed selective LP suppression with MASP-2 blockade and AP suppression with MASP-3 blockade, whereas dual inhibition maximally reduced both pathways and their downstream complement effectors. Kidney transcriptomics demonstrated broad down-regulation of complement, coagulation, and inflammatory gene networks. Together, these findings indicate that bispecific MASP-2/3 blockade provides robust complement-directed protection in established LN and may represent an effective therapeutic strategy for complement-mediated kidney disease.

Source: Clinical & Experimental Immunology

DOI: 10.1093/cei/uxag031

Authors: Tianqi Tu, Chuqiao Wang, Zhong Li, Wenyan Fu, Ying Tan, Minghui Zhao

Institutions: Ministry of Education of the People's Republic of China, Peking University, Peking University First Hospital

Language: English

Topic: Complement system in diseases

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Peking University First Hospital, Chinese Academy of Medical Sciences, Beijing Municipal Natural Science Foundation, National Key Research and Development Program of China