Proteolytic profiling of human plasma reveals an immunoactive complement C3 fragment

ABSTRACT: Dysregulated proteolysis is central to autoimmune pathogenesis. The complement cascade, a major protease network, generates fragments that modulate immunity and tissue injury. We developed a scalable blood plasma N-terminomics workflow that markedly expands detection of proteolytic events in vitro and in vivo. Applied to 143 systemic lupus erythematosus (SLE) patients, Multi-Omics Factor Analysis (MOFA) linked N-terminal signatures to immunological and clinical heterogeneity. This revealed a previously unrecognized complement fragment, C3-LHF1, encompassing the C345C domain and rivaling the abundance of canonical fragments like C3a and C3b. C3-LHF1 correlated with renal function and remission in lupus nephritis, and exhibited dual functions: inhibiting classical and lectin complement pathw

SUBMITTER: Fatih Demir 

PROVIDER: S-SCDT-10_1038-S44318-025-00598-8 | biostudies-other |

REPOSITORIES: biostudies-other