dc.date.accessioned | 2022-02-02T18:38:10Z | |
dc.date.available | 2022-02-02T18:38:10Z | |
dc.date.created | 2022-01-07T12:10:55Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Gramstad, Olav Rogde Kandanur, Sai Priya Sarma Etscheid, Michael Nielsen, Erik Waage Kanse, Sandip . Factor VII activating protease (FSAP) is not essential in the pathophysiology of angioedema in patients with C1 inhibitor deficiency. Molecular Immunology. 2021, 142, 95-104 | |
dc.identifier.uri | http://hdl.handle.net/10852/90442 | |
dc.description.abstract | Background
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.
Objective
To investigate the interaction between FSAP and C1 inhibitor (C1Inh) and evaluate the potential role of FSAP in HAE with C1Inh deficiency.
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.
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.
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. | |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Factor VII activating protease (FSAP) is not essential in the pathophysiology of angioedema in patients with C1 inhibitor deficiency | |
dc.type | Journal article | |
dc.creator.author | Gramstad, Olav Rogde | |
dc.creator.author | Kandanur, Sai Priya Sarma | |
dc.creator.author | Etscheid, Michael | |
dc.creator.author | Nielsen, Erik Waage | |
dc.creator.author | Kanse, Sandip | |
cristin.unitcode | 185,51,12,10 | |
cristin.unitname | Seksjon for Biokjemi | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1976496 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular Immunology&rft.volume=142&rft.spage=95&rft.date=2021 | |
dc.identifier.jtitle | Molecular Immunology | |
dc.identifier.volume | 142 | |
dc.identifier.startpage | 95 | |
dc.identifier.endpage | 104 | |
dc.identifier.doi | https://doi.org/10.1016/j.molimm.2021.11.019 | |
dc.identifier.urn | URN:NBN:no-93044 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0161-5890 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/90442/1/1-s2.0-S0161589021003357-main.pdf | |
dc.type.version | PublishedVersion | |
dc.relation.project | NFR/251239 | |