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dc.contributor.authorGramstad, Olav Rogde
dc.contributor.authorKandanur, Sai Priya Sarma
dc.contributor.authorEtscheid, Michael
dc.contributor.authorNielsen, Erik Waage
dc.contributor.authorKanse, Sandip
dc.date.accessioned2022-02-08T09:26:23Z
dc.date.available2022-02-08T09:26:23Z
dc.date.issued2021-12-29
dc.description.abstractBackground: Excessive bradykinin (BK) generation from high molecular weight kininogen (HK) by plasma kallikrein (PK) due to lack of protease inhibition is central to the pathophysiology of hereditary angioedema (HAE). Inadequate protease inhibition may contribute to HAE through a number of plasma proteases including factor VII activating protease (FSAP) that can also cleave HK.<p> <p>Objective: To investigate the interaction between FSAP and C1 inhibitor (C1Inh) and evaluate the potential role of FSAP in HAE with C1Inh deficiency.<p> <p>Materials and methods: Plasma samples from 20 persons with HAE types 1 or 2 in remission were studied and compared to healthy controls. We measured and compared antigenic FSAP levels, spontaneous FSAP activity, FSAP generation potential, activation of plasma pre-kallikrein (PPK) by FSAP, and the formation of FSAP-C1Inh and FSAP-alpha2-antiplasmin (FSAP-α2AP) complexes. Furthermore, we measured HK cleavage and PK activation after activation of endogenous pro-FSAP and after addition of exogenous FSAP.<p> <p>Results: In plasma from HAE patients, there is increased basal FSAP activity compared to healthy volunteers. HAE plasma exhibits decreased formation of FSAP-C1Inh complexes and increased formation of FSAP-α2AP complexes in histone-activated plasma. Although exogenous FSAP can cleave HK in plasma, this was not seen when endogenous plasma pro-FSAP was activated with histones in either group. PK was also not activated by FSAP in plasma.<p> <p>Conclusion: In this study, we established that FSAP activity is increased and the pattern of FSAP-inhibitor complexes is altered in HAE patients. However, we did not find evidence suggesting that FSAP contributes directly to HAE attacks.en_US
dc.identifier.citationGramstad OR, Kandanur, Etscheid, Nielsen, Kanse. Factor VII activating protease (FSAP) is not essential in the pathophysiology of angioedema in patients with C1 inhibitor deficiency. Molecular Immunology. 2021;142:95-104en_US
dc.identifier.cristinIDFRIDAID 1976496
dc.identifier.doi10.1016/j.molimm.2021.11.019
dc.identifier.issn0161-5890
dc.identifier.issn1872-9142
dc.identifier.urihttps://hdl.handle.net/10037/23947
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalMolecular Immunology
dc.relation.projectIDNorges forskningsråd: 251239en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMED2-FRIPRO/251239/Norway/Development of novel therapeutic and diagnostic strategies in ischemic stroke based on Factor VII activating protease/FSAP/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.titleFactor VII activating protease (FSAP) is not essential in the pathophysiology of angioedema in patients with C1 inhibitor deficiencyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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