Inhibitor development: patient-determined risk factors.

The reasons that inhibitory factor VIII antibodies develop in only a fraction of patients with haemophilia A remain unclear, but studies of genetically related subjects have indicated that the immunological outcome of replacement therapy is to a large extent determined by patient-related risk factors. Non-genetic factors will also influence the inhibitor risk, since events challenging the immune system will elicit and stimulate immune regulatory processes with the potential of modifying the immune response. Further insight into the immunological pathways and risk factors involved will be important in order to better predict and prevent this complication. This review will briefly summarize the data obtained to date in unrelated and related subjects in the Malmö International Brother Study (MIBS) regarding genetic factors and discuss how these factors might interact with non-genetically determined factors and events.