Targeting the complement lectin pathway with a highly specific MASP-2 inhibitor protects against renal ischemia-reperfusion injury.

ABSTRACT: Renal ischemia-reperfusion injury (IRI) is a common complication in several clinical scenarios including kidney transplantation. Mannan-binding lectin-associated serine proteinase (MASP)-2 is essential for activation of the complement lectin pathway, which has been implicated in the pathogenesis of renal IRI and therefore represents a potential therapeutic target. We developed a new, affinity-enhanced MASP-2 inhibitor, EVO24, by directed evolution of the D2 domain of human tissue factor pathway inhibitor. EVO24 was fused with a human IgG1-Fc to create the homodimer EVO24L, which potently and selectively inhibited the lectin pathway in human and mouse serum in vitro. EVO24L was tested in a mouse model of unilateral warm renal IRI. EVO24L administered before and after ischemia significantly

SUBMITTER: Bongoni AK 

PROVIDER: S-EPMC12037010 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature