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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.<\/jats:p>","DOI":"10.1093\/cei\/uxag031","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:46:39Z","timestamp":1779968799000},"source":"Crossref","is-referenced-by-count":0,"title":["Bispecific MASP-2\/3 antibody provides superior renoprotection over monotherapy in pristane-induced lupus nephritis"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7106-6483","authenticated-orcid":false,"given":"Tianqi","family":"Tu","sequence":"first","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital , Beijing 100034 ,","place":["China"]},{"name":"Institute of Nephrology, Peking University , Beijing 100034 ,","place":["China"]},{"name":"Key Laboratory of Renal 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,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Fu","sequence":"additional","affiliation":[{"name":"Staidson (Beijing) Biopharmaceuticals Co., Ltd , Beijing 100176 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8139-5758","authenticated-orcid":false,"given":"Ying","family":"Tan","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Peking University First Hospital , Beijing 100034 ,","place":["China"]},{"name":"Institute of Nephrology, Peking University , Beijing 100034 ,","place":["China"]},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China , Beijing 100034 ,","place":["China"]},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China , Beijing 100034 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