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dc.contributor.authorMacpherson, Magnhild Eide
dc.contributor.authorHalvorsen, Bente
dc.contributor.authorYndestad, Arne
dc.contributor.authorUeland, Thor
dc.contributor.authorMollnes, Tom Eirik
dc.contributor.authorBerge, Rolf Kristian
dc.contributor.authorRashidi, Azita
dc.contributor.authorOtterdal, Kari
dc.contributor.authorGregersen, Ida
dc.contributor.authorKong, Xiang Yi
dc.contributor.authorHolven, Kirsten Bjørklund
dc.contributor.authorAukrust, Pål
dc.contributor.authorFevang, Børre
dc.contributor.authorJørgensen, Silje Fjellgård
dc.date.accessioned2019-09-17T11:49:40Z
dc.date.available2019-09-17T11:49:40Z
dc.date.issued2019-07-01
dc.description.abstractCommon variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency, characterized by inadequate antibody responses and recurrent bacterial infections. Paradoxically, a majority of CVID patients have non-infectious inflammatory and autoimmune complications, associated with systemic immune activation. Our aim was to explore if HDL, known to have anti-inflammatory properties, had impaired function in CVID patients and thereby contributed to their inflammatory phenotype. We found reduced HDL cholesterol levels in plasma of CVID patients compared to healthy controls, particularly in patients with inflammatory and autoimmune complications, correlating negatively with inflammatory markers CRP and sCD25. Reverse cholesterol transport capacity testing showed reduced serum acceptance capacity for cholesterol in CVID patients with inflammatory and autoimmune complications. They also had reduced cholesterol efflux capacity from macrophages to serum and decreased expression of ATP-binding cassette transporter ABCA1. Human HDL suppressed TLR2-induced TNF release less in blood mononuclear cells from CVID patients, associated with decreased expression of transcriptional factor ATF3. Our data suggest a link between impaired HDL function and systemic inflammation in CVID patients, particularly in those with autoimmune and inflammatory complications. This identifies HDL as a novel therapeutic target in CVID as well as other more common conditions characterized by sterile inflammation or autoimmunity.en_US
dc.description.sponsorshipSouth-Eastern Norway Regional Health Authorityen_US
dc.descriptionSource at <a href=https://doi.org/10.1038/s41598-019-45861-1>https://doi.org/10.1038/s41598-019-45861-1. </a>en_US
dc.identifier.citationMacpherson, M.E., Halvorsen, B., Yndestad, A., Ueland, T., Mollnes, T.E., Berge, R.K. ... Jørgensen, S.F. (2019). Impaired HDL function amplifies systemic inflammation in common variable immunodeficiency. <i>Scientific Reports, 9</i>:9427. https://doi.org/10.1038/s41598-019-45861-1en_US
dc.identifier.cristinIDFRIDAID 1721488
dc.identifier.doi10.1038/s41598-019-45861-1
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/10037/16212
dc.language.isoengen_US
dc.publisherNature Researchen_US
dc.relation.journalScientific Reports
dc.relation.projectIDinfo:eu-repo/grantAgreement/RCN/FRIMED2/249732/Norway/The DNA glycosylase Neil3 - a metabolic sensor in atherogenesis//en_US
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.subjectDyslipidaemiasen_US
dc.subjectMolecular medicineen_US
dc.subjectPrimary immunodeficiency disordersen_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleImpaired HDL function amplifies systemic inflammation in common variable immunodeficiencyen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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