We analyzed two large anti-β2GPI IgG positive cohorts, to investigate whether different domain binding affects anti-β2GPI IgG assay testing and APS diagnosis.<h4>Methods</h4>The presence of anti-DI and anti-DIV/DV antibodies (by chemiluminescence (CLIA) and in-house ELISA, respectively) was searched in an APS ACTION (n.191) and Italian validation (n.105) cohorts. This evidence concerns the gene APOH and autoimmune polyendocrinopathy.