Please use this identifier to cite or link to this item: http://elea.unisa.it:8080/xmlui/handle/10556/1382
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dc.contributor.authorRisitano, Antonio M.-
dc.date.accessioned2014-06-04T10:13:25Z-
dc.date.available2014-06-04T10:13:25Z-
dc.date.issued2014-
dc.identifier.citationRisitano AM. Anti-complement treatment in paroxysmal nocturnal hemoglobinuria: where we stand and where we are going. Translational Medicine @ UniSa 2014;8(6):43-52en_US
dc.identifier.issn2239-9747en_US
dc.identifier.urihttp://hdl.handle.net/10556/1382-
dc.identifier.urihttp://dx.doi.org/10.14273/unisa-231-
dc.description.abstractParoxysmal nocturnal hemoglobinuria (PNH) is a clonal, non-malignant, hematological disorder characterized by the expansion of hematopoietic stem cells and progeny mature blood cells which are deficient in some surface proteins, including the two complement regulators CD55 and CD59. PNH is the paradigm of diseases implying complement dysregulation as main pathogenic mechanism; in fact, PNH erythrocytes are uncapable to modulate on their surface physiologic complement activation, which eventually leads to the typical clinical hallmark of PNH – the chronic complement-mediated intravascular anemia. Indeed, due to the lack of CD55 complement is continuously activated on erythrocyte surface, which subsequently enables the terminal lytic complement because of the lack of CD59, finally resulting in erythrocyte lysis. The availability of eculizumab as the first complement inhibitor for clinical use renewed the interest for this rare hematological disease. Indeed, in the last decad the anti-C5 monoclonal antibody has proven effective for the treatment of PNH, resulting in a sustained control of complement-mediated intravascular hemolysis, with a remarkable clinical benefit. Anti-complement treatment allowed transfusion independence in at least half of PNH patients receiving eculizumab, with adequate control of all hemolysis-associated symptoms even in almost all remaining patients. In addition, the risk of thromboembolic events – an other clinical hallmark of PNH, which significantly affects prognosis and survival – seems substantially reduced on eculizumab treatment, apparently resulting in improved survival. Even with all these remarkable effects, eculizumab treatment does not result in hemoglobin normalization, and most patients remain anemic. It has been demonstrated that this is due to persistent activation of the early phases of complement activation (upstream the C5), leading to complement-mediated extravascular hemolysis. Ongoing researches are focusing on possible strategies to improve current anti-complement therapies, aiming to develop second-generation complement therapeutics. Here we review PNH and its complement-mediated pathophysiology, summarizing available data on anti-complement treatment; we’ll also discuss recent pathogenic insights which drive the development of novel strategies of complement inhibition.en_US
dc.format.extentP. 43-52en_US
dc.language.isoenen_US
dc.sourceUniSa. Sistema Bibliotecario di Ateneoen_US
dc.subjectParoxysmal nocturnal hemoglobinuriaen_US
dc.subjectComplement alternative pathwayen_US
dc.subjectComplement component 3en_US
dc.subjectComplement component 5en_US
dc.subjectEculizumaben_US
dc.subjectComplement therapeuticsen_US
dc.subjectC3-targeted therapyen_US
dc.titleAnti-complement treatment in paroxysmal nocturnal hemoglobinuria: where we stand and where we are goingen_US
dc.typeArticleen_US
Appears in Collections:Translational Medicine @ UniSa. Vol.8 (jan.-mar. 2014)

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