Vimmune Ec Injury

EC-reactive antibodies have been found in patients suffering from disorders characterized by vasculitis or thrombosis (for review: see Praprotnik et al., 2001a; Meroni et al., 2005). The best-studied example is allograft rejection, a setting in which there is extensive evidence for AECA, in part directed at carbohydrate antigens that regulate procoagulant activity in vitro (Saadi and Platt, 1995; Diujvestijn et al., 2000). AECA have also been identified in patients with hyper-acute and acute graft rejection, systemic lupus erythematosus (Constans et al., 2003), antiphospholipid antibody syndrome (Cesarman-Maus et al., 2006), and thrombotic thrombocytopenic purpura (Praprotnik et al., 2001b). What is curious is the extraordinary diversity of the clinical syndromes associated with AECA. Also of interest, the target cells used in most assays (i.e., ECs derived from human umbilical vein [HUVEC]), are not known to be affected by immune vascular injury in the clinical setting. This suggests that the expression of the target antigen(s) is highly restricted in vivo, reflecting either regional differences in the composition of the vascular bed (microvascular or macrovascular) or, perhaps, indicating distinct responses to injury and inflammation. Alternatively, these AECA could represent a surrogate marker for other pathogenic antibodies, or the capacity of the affected vasculature is a critical determinant of whether thrombosis develops.

Several effects of AECA that could contribute to thrombosis include cell lysis or apoptosis (Bordron et al., 2001), induction of cytokine secretion and promotion of leukocyte adhesion (Del Papa et al., 1997), enhancement of vascular permeability (Tinckam and Chandraker, 2006), acceleration of procoagulant reactions (Saadi et al., 1995), and reduction in the expression of heparan sulfate (Nathan and Ihrcke, 1996). The reason why some antibodies promote thrombosis (e.g., HIT antibodies), whereas others induce primarily a necrotizing vasculitis, remains unresolved, but may relate directly to the biological functions of heparin and PF4.

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