Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development.

Antiphospholipid antibodies (aPL) in primary or secondary antiphospholipid syndrome (APS) are a major cause for acquired thrombophilia. Here we show that specific inhibition of the TF coagulation initiation complex with nematode anticoagulant protein c2 (NAPc2) prevents the the development of persistent aPL and circulating phospholipid-reactive B1 cells in latent viral infection and lupus prone MRL-lpr mice. NGS mRNA profiling of splenic DC in lupus mice treated with NAPc2 versus saline control uncovered a suppression of dendritic cell activation in the spleen. Overall design: NGS sequencing of splenic DCs used spleens digested with collagenase II and DNase I followed by dissociated cell enrichment on an Optiprep density gradient and FACS of live DCs identified by MHCII and CD11c in the CD3/CD19/NK1.1 negative population. DC RNA of 4 saline and 4 NAPc2 treated mice was sequenced by Novogene and mapped to the GRCm39 mouse genome with STAR on the fly.