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Search: (swepub) lar1:(umu) spr:eng lar1:(lnu) > (2020-2024) > A survey of ficolin...

  • Lindelöf, LinneaUppsala University,Karolinska Institutet,Uppsala universitet,Vaskulärbiologi,Bo Nilsson,Uppsala Univ, Sweden (author)

A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile

  • Article/chapterEnglish2024

Publisher, publication year, extent ...

  • Elsevier,2024
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:lnu-128256
  • https://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-128256URI
  • https://doi.org/10.1016/j.jaut.2023.103166DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-220019URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-227429URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524604URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-201482URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:155038138URI
  • https://lup.lub.lu.se/record/baba9340-0f9e-4781-a4cb-eaccf3e9b0edURI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|Agnes and Mac Rudberg Foundation; Goran Gustafsson Foundation; Jeansson Foundation; Swedish Rheumatism Association; King Gustaf V 80-year Anniversary Foundation; Swedish Society of Medicine; Swedish Research Council for Medicine and Health [2018-02551, 2018-02399, 2020-05762, 2021-02252, 2018-02535, 2022-00783]; Gustafsson Foundation; Swedish Heart-Lung Foundation; ALF; Wallenberg Scholarship; National Bioinformatics Infrastructure Sweden (NBIS); Swedish Research Council [2018-05973, 2022-06725]
  • The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.

Subject headings and genre

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  • Rantapää-Dahlqvist, SolbrittUmeå universitet,Reumatologi,Umeå University, Sweden,Umeå Univ, Dept Publ Hlth & Clin Med Rheumatol, Umeå, Sweden.(Swepub:umu)sora0001 (author)
  • Lundtoft, ChristianUppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden(Swepub:uu)chrlu632 (author)
  • Sandling, Johanna K.Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden(Swepub:uu)josan062 (author)
  • Leonard, Dag,1975-Uppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden(Swepub:uu)dagle338 (author)
  • Sayadi, AhmedUppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden(Swepub:uu)ahmsa102 (author)
  • Rönnblom, LarsUppsala University,Uppsala universitet,Reumatologi,Uppsala Univ, Sweden(Swepub:uu)larsronn (author)
  • Enocsson, HelenaLinköping University,Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland(Swepub:liu)helen05 (author)
  • Sjöwall, ChristopherLinköping University,Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland(Swepub:liu)chrsj93 (author)
  • Jönsen, AndreasLund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)reum-ajo (author)
  • Bengtsson, Anders A.Lund University,Lunds universitet,Lund SLE Research Group,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital(Swepub:lu)reum-abe (author)
  • Hong, Mun-Gwan,1976-Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm University, Sweden;Sci Life Lab, Sweden,Stockholm Univ, Dept Biochem & Biophys, Natl Bioinformat Infrastruct Sweden, Sci Life Lab, Stockholm, Sweden.(Swepub:su)muho4116 (author)
  • Diaz-Gallo, Lina-MarcelaKarolinska Institute,Karolinska University Hospital (author)
  • Bianchi, MatteoUppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden(Swepub:uu)matbi944 (author)
  • Kozyrev, Sergey V.Uppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden(Swepub:uu)sekoz957 (author)
  • Lindblad-Toh, KerstinUppsala University,Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Broad Inst MIT & Harvard, Cambridge, MA USA,Uppsala Univ, Sweden; Broad Inst MIT & Harvard, MA USA,Broad Institute(Swepub:uu)kerli865 (author)
  • Nilsson Ekdahl, KristinaUppsala University,Linnaeus University,Uppsala universitet,Linnéuniversitetet,Institutionen för kemi och biomedicin (KOB),Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Linnaeus Center for Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden,Linnaeus Ctr Biomat Chem, BMC,Vaskulärbiologi,Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden,Uppsala Univ, Sweden; Linnaeus Univ, Sweden(Swepub:uu)krisnil (author)
  • Nilsson, BoUppsala University,Uppsala universitet,Vaskulärbiologi,Uppsala Univ, Sweden(Swepub:uu)bonils (author)
  • Gunnarsson, IvaKarolinska Institute,Karolinska Institutet,Karolinska University Hospital (author)
  • Svenungsson, ElisabetKarolinska Institute,Karolinska Institutet,Karolinska University Hospital (author)
  • Eriksson, Oskar,1984-Uppsala University,Uppsala universitet,Vaskulärbiologi,Uppsala Univ, Sweden(Swepub:uu)osker931 (author)
  • Uppsala universitetVaskulärbiologi (creator_code:org_t)
  • ImmunoArray consortium

Related titles

  • In:Journal of Autoimmunity: Elsevier1430896-84111095-9157

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