Induction of immune tolerance to RBC, platelet, and neutrophil antigens and IgA

Antibodies to red blood cell (RBC), platelet, and neutrophil antigens, and IgA may cause serious clinical problems. With a few exceptions, preventing these conditions is a matter of limiting exposure to the foreign antigen while treatment consists of managing the consequences. Might immune tolerance induction (ITI) be possible and beneficial in these situations? Neonatal exposure to antigens is known to induce central tolerance. However central tolerance may not be absolute. Factors that determine whether an antibody will be produced in response to an antigen are not well understood but include the appropriate expression of major histocompatibility complex-class II and/or co-stimulatory molecules on dendritic cells, the presence or absence of adjuvants and whether or not the antigen is presented together with agonists for the toll-like receptor. Modifying these may prevent alloimmunization. Peripheral tolerance, in sensitized individuals, as routinely used in patients with allergic/anaphylactic reactions, those with haemophilia A or B with inhibitors and acquired haemophilia, may also be possible. Briefly, monitored, graded, increasing exposure to the antigen of interest with or without additional immunosuppression is used. Neither central nor peripheral ITI has been tried or suggested for individuals sensitizable or sensitised to RBC, platelet, and neutrophil antigens, or IgA. Theoretically, this is possible and may be of benefit.