Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xenotransplantation using pig organs could solve the significant increasing shortage of donor organs for allotransplantation. In the last two decades, major progress has been made in understanding the xenoimmunobiology of pig-to-nonhuman primate transplantation, and today we are close to clinical trials. The ability to genetically engineer pigs, such as human decay-accelerating factor (hDAF), CD46 (membrane cofactor protein), or alpha1,3-galactosyltransferase gene-knockout (GT-KO), has been a significant step toward the clinical application of xenotransplantation. Using GT-KO pigs and novel immunosuppressant agents, 2 to 6 months' survival of heterotopic heart xenotransplants has been achieved. In life-supporting kidney xenotransplantation, promising survival of close to 3 months has been achieved. However, liver and lung xenotransplantations do not have such encouraging survival as kidney and heart xenotransplantation. Although the introduction of hDAF and GT-KO pigs largely overcame hyperacute rejection, acute humoral xenograft rejection (AHXR) remains a challenge to be overcome if survival is to be increased. In several studies, when classical AHXR was prevented, thrombotic microangiopathy and coagulation dysregulation became more obvious, which make them another hurdle to be overcome. The initiating cause of failure of pig cardiac and renal xenografts may be antibody-mediated injury to the endothelium, leading to the development of microvascular thrombosis. Potential contributing factors toward the development of the thrombotic microangiopathy include: 1) the presence of preformed anti-non-Gal antibodies, 2) the development of very low levels of elicited antibodies to non-Gal antigens, 3) natural killer cell or macrophage activity, and 4) inherent coagulation dysregulation between pigs and primates. The breeding of pigs transgenic for an 'anticoagulant' or 'anti-thrombotic' gene, such as human tissue factor pathway inhibitor, hirudin, or CD39, or lacking the gene for the prothrombinase, fibrinogen-like protein-2, is anticipated to inhibit the change in the endothelium to a procoagulant state that takes place in the pig organ after transplantation. A further limitation for organ xenotransplantation is the potential for cross-species infection. As far as exogenous viruses are concerned, porcine cytomegalovirus has been detected in the tissues of recipient non-human primates, although no invasive disease was reported. Until today, no formal evidence has been presented from in vivo studies in non-human primates or from humans exposed to pig organs, tissues, or cells that porcine endogenous retroviruses infect primate cells. Xenotransplantation is a potential answer to the current organ shortage. Its future depends on; 1) further genetic modification of pigs, 2) the introduction of novel immunosuppressive agents that target the innate immune system and plasma cells, and 3) the development of clinically-applicable methods to induce donor-specific tolerance.
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PMID:Xenotransplantation of solid organs in the pig-to-primate model. 1895 43

A 9-year-old boy with pallor and macrohematuria showed hemolytic anemia, thrombocytopenia and renal failure. There was no history of diarrhea and the stool culture was negative. A diagnosis of atypical hemolytic uremic syndrome (HUS) was confirmed; however, the cause of the prolonged activated partial thromboplastin time (APTT) was unknown. Plasma exchange and hemodialysis were performed because of progressive hemolytic anemia and renal dysfunction. Fresh frozen plasma was administered frequently to correct the prolonged APTT after hemolysis was controlled and C3 levels had recovered. Factor H (FH) and factor I (IF) levels were normal and we did not detect mutations of FH, IF and membrane cofactor protein. Further investigation revealed the presence of anti-FH antibody in the patient's plasma and a deficiency of coagulation factor XII. Analysis of the patient's coagulation system displayed <3% functional activity of factor XII, whereas levels of other coagulation factors were within the normal range. Two novel mutations (W222G and R447S) were identified upon analysis of the factor XII gene in this patient. Moreover, further investigation revealed that compound heterozygous mutations were present in two of the patient's three siblings, while the third sibling only had a mutation at W222G. The patient was treated for atypical HUS; however, no treatment was required for factor XII deficiency as he did not display a hemorrhagic tendency. We report here a rare case of atypical HUS due to anti-FH antibody presenting with a coagulation factor XII deficiency.
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PMID:A case of atypical hemolytic uremic syndrome due to anti-factor H antibody in a patient presenting with a factor XII deficiency identified two novel mutations. 2127 Dec 73