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Immune tolerance in haemophilia: the long journey to the fork in the road
Author(s) -
DiMichele Donna M.
Publication year - 2012
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12028
Subject(s) - haemophilia , medicine , immunology , immune tolerance , incidence (geometry) , intensive care medicine , immune system , pediatrics , physics , optics
Summary Antibody eradication is the ultimate goal of inhibitor management. The only clinically proven strategy for achieving antigen‐specific tolerance to factor VIII is immune tolerance induction ( ITI ). Our knowledge about ITI in haemophilia A and B was, historically, derived from small cohort studies and retrospective national and international ITI registries. Practice is now further influenced by prospective cohort data, and the results of a single prospective randomized international ITI trial. However, due to the low incidence of inhibitors in haemophilia B , there are few comparable data from which to develop a useful evidence‐based approach to the prevention and eradication of factor IX inhibitors. The lack of an effective strategy is particularly problematic given the morbidity associated with the unique occurrence of allergic and anaphylactic reactions that often herald factor IX antibody development and preclude effective eradication. This paper will discuss our current understanding of immune tolerance outcome and outcome predictors for haemophilia A and B ; review the current consensus practice recommendations for ITI ; and summarize the emerging body of immunological science relating to antibody formation and tolerance. It will conclude by suggesting how our knowledge might inform the future investigative priorities impacting the therapeutic and preventative tolerance strategies of tomorrow.