Rejection hyperacute

Hyperacute rejection—Very rapid attack of foreign cells or organs caused by binding protein of the body s immune system. 

Apart from its potent antiproliferative activity, tetrasaccharide 15 was effective in blocking human complement in vitro and inhibited the release of heparan sulfate from cardiac microvascular endothelial cells. To overcome hyperacute rejection, the tetrasaccharide has been investigated in a guinea pig to rat cardiac xenotransplantation model and significantly prolonged the survival of heart recipients when compared to control and heparin treated groups [46]. 

The complement system is a humoral effector of inflammation which is activated by a cascade mechanism through the classical and/or alternative pathway [62]. Activation of the system is normally beneficial for the host. However, excessive activation may evoke pathological reaction in a variety of immunological and degenerative diseases and hyperacute rejection in transplantation. Therefore, the modulation of complement activity should be useful in the therapy of inflammatory diseases. 

The rejection period for a graft varies from tissue to tissue and the type of immune response involved in this process. They are divided into three types hyperacute rejection, acute rejection and chronic rejection. 

There are only a few reports of hyperacute rejection after liver transplantation. This may be due to the ability of the Kupffer cells to remove cytotoxic antibodies formed against the graft because of their reticuloendothelial function. Acute rejection is the more common form of rejection, which is manifested within 7-10 days after liver transplantation and exhibits symptoms of fever, malaise, pain, tachycardia and hepatomegaly. Mental disorientation in patients has also been reported during acute rejection. Liver biopsy is performed to confirm acute rejection that is generally mild in nature, and lymphocytic infiltration is observed in the portal tracts under the endothelium of the sinusoids. 

Vic G, Scigelova M, Hastings JJ, Howarth OW, Crout DHG. Glycosidase-catalysed synthesis of oligosaccharides trisaccharides with the a-D-gal-(1 3)-D-gal terminus responsible for the hyperacute rejection response in cross-species transplant rejection 34. from pigs to man. Chem. Commun. 1996 12 1473-1474. 

Hanessian, S, Saavedra, O M, Mascitti, V, Marterer, W, Oehrlein, R, Mak, C-P, Practical syntheses of B disaccharide and linear B type 2 trisaccharide — non-primate epitope markers recognized by human anti-a-Gal antibodies causing hyperacute rejection of xenotransplants. Tetrahedron, 57, 3267-3280, 2001. 

Hyperacute rejection occurs within minutes to hours following revascularization of a graft. The cause is due to the presence of preformed circulating antibody (IgG) that reacts with the blood cell antigens (the ABO system), or MHCI molecules or other poorly defined antigens. This should now be a rare event clinically as recipients are tested (cross-matched) before transplantation for the presence of antibodies reactive with cells of the donor. 

T. Zhu and G.-J. Boons, Two-directional, convergent synthesis of a pentasaccharide that is involved in the hyperacute rejection response in xenotransplantation from pig to man, J. Chem. Soc., Perkin Trans., 1 (1998) 857-862. 

The trisaccharide has been found to be responsible for hyperacute rejections in the xenotransplantation area [10, 79]. The pig enzyme has been cloned and overexpressed in insect cells, and is currently being evaluated for preparative use [80]. It tolerates a wide range of non-natural acyl replacements of the A-acetyl group of the penultimate GlcNAc moiety (Table 6) [81]. 

Hyperacute rejection may occur when preformed donor-specific antibodies are present in the recipient at the time of the transplant and may be evident within minutes of the transplant procedure. Hyperacute rejection can be induced by immunoglobulin G (IgG) antibodies that bind to antigens on the vascular endothelium, such as class I MHC, ABO, and vascular endothelial cell antigens. Tissue damage can be mediated through antibody-dependent, cell-mediated cytotoxicity or through activation of the complement cascade. The ischemic damage to the microvasculature rapidly produces tissue necrosis. 

Hyperacute rejection has become uncommon in kidney and heart transplants because transplant donors are matched for ABO blood groups and crossmatch testing is done to determine the presence of donor-specific lymphocytotoxic antibodies. A positive crossmatch presents a serious risk for graft failure even if hyperacute rejection does not occur. A negative lymphocytotoxicity crossmatch does not entirely rule out the possibility of hyperacute rejection because non-MHC antigens on the vascular endothelium can serve as targets of donor-specific antibodies. 

Hyperacute rejection rarely occurs in patients receiving a liver transplant. The liver s special status for transplantation is not fully understood, but the local release of cytokines may alter the immunologic reaction taking place in the liver. Early graft dysfunction is treated with supportive care and retransplantation if possible. 

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