This is a request for support of an international scientific meeting on inhibitors (antibodies) to blood co- angulation factors to be held in November 1993 in Chapel Hill, NC, co-sponsored by the Center for Thrombosis and Hemostasis at the University of North Carolina at Chapel Hill (UNC-CH) and the UNC-CH Office of Continuing Medical Education. In November 1983 the first International Symposium on Factor VIII Inhibitors was held in Farmington, CT, jointly sponsored by The University of Connecticut Health Center, The National Hemophilia Foundation and the NHLBI. It addressed the immunobiology of the human immune response to therapeutically infused coagulation factors (Factors VIII and IX). Although the succeeding ten years have brought new therapies for hemophilia patients with inhibitors, such patients continue to represent a difficult clinical problem. Although advances in the preparation of Factor VIII and Factor IX concentrates have yielded highly purified, viral free materials 20 to 25% of hemophilia A patients continue to develop inhibitors. With the imminent advent of gene therapy for the hemophilias, an area of particular interest to the NHLBI, careful consideration of the factors predisposing patients to develop inhibitors and methods for suppressing this unwanted response in a specific manner become all the more critical. Minimally, we must be able to predict those patients at particular risk prior to undertaking gene therapy to maximize the cost/benefit ratio for the patient and society. The purpose of the proposed meeting is to provide a forum in which the most up-to- date concepts on the nature and control of the human immune response will be presented and discussed in conjunction with an overview of what is known about the immunobiology and the therapy of inhibitors. The interaction of expert immunogists and clinicians/researchers interested in the inhibitors problem will help to delineate important areas of future research and offer potential new therapeutic approaches which may be critical for the success of gene therapy for the hemophilias.
