Monoclonal antibody 26 cross-reactive with β2-glycoprotein I affects human trophoblast invasion in vitro

ObjectiveMonoclonal antibody 26 (MAb 26) raised against tetanus toxoid has documented cross-reactivity with β2-glycoprotein I. Passive introduction of this antibody in mice results in an antiphospholipid syndrome-like condition. We investigated the effects of MAb 26 on first trimester human trophoblast in vitro.Study designBinding of MAb 26 to placental tissue trophoblast, isolated cytotrophoblast and HTR-8/SVneo cells was analyzed by immunohisto(cyto)chemistry. Possible effects on cell invasion in vitro were assessed by Matrigel assay. Effects on cell viability were assessed by MTT test. A possibility that MAb 26 induces change in levels of effector molecules important for cell invasion was investigated. Integrin subunits α1, α5 and β1, and galectin-1, were analyzed by qPCR and Western blot. Metalloproteinases -2 and -9 were assessed by gelatin zymography.ResultsImmunohisto(cyto)chemistry showed binding of MAb 26 to placental tissue trophoblast, isolated cytotrophoblast and HTR-8/SVneo cells. The antibody had a significant inhibitory effect on cell invasion by both isolated cytotrophoblast and HTR-8/SVneo. The antibody induced significant decrease in protein levels of metalloproteinases, integrin subunit α1 and galectin-1. Cell viability was not affected.ConclusionMAb 26 reduces trophoblast invasion in vitro through decreased levels of metalloproteinases-2 and -9, integrin α1 and galectin-1.