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A survey of ficolin...
A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile
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- Lindelöf, Linnea (author)
- Karolinska Institutet,Uppsala universitet,Vaskulärbiologi,Bo Nilsson,Uppsala Univ, Sweden
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- Rantapää-Dahlqvist, Solbritt (author)
- Umeå universitet,Reumatologi,Umeå University, Sweden,Umeå Univ, Dept Publ Hlth & Clin Med Rheumatol, Umeå, Sweden.
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- Lundtoft, Christian (author)
- Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Sandling, Johanna K. (author)
- Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Leonard, Dag, 1975- (author)
- Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Sayadi, Ahmed (author)
- Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Rönnblom, Lars (author)
- Uppsala universitet,Reumatologi,Uppsala Univ, Sweden
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- Enocsson, Helena (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
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- Sjöwall, Christopher (author)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Reumatologiska kliniken i Östergötland
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- Jönsen, Andreas (author)
- Department of Clinical Sciences Lund, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden,Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden.
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- Bengtsson, Anders A. (author)
- Department of Clinical Sciences Lund, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden,Lund Univ, Skane Univ Hosp, Dept Clin Sci Lund, Rheumatol, Lund, Sweden.
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- Hong, Mun-Gwan, 1976- (author)
- 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.
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- Diaz-Gallo, Lina-Marcela (author)
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden,Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Rheumatol, Stockholm, Sweden.
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- Bianchi, Matteo (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden
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- Kozyrev, Sergey V. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Uppsala Univ, Sweden
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- Lindblad-Toh, Kerstin (author)
- 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
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- Nilsson Ekdahl, Kristina (author)
- 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
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- Nilsson, Bo (author)
- Uppsala universitet,Vaskulärbiologi,Uppsala Univ, Sweden
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- Gunnarsson, Iva (author)
- Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden,Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Rheumatol, Stockholm, Sweden.
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- Svenungsson, Elisabet (author)
- Karolinska Institutet
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- Eriksson, Oskar, 1984- (author)
- Uppsala universitet,Vaskulärbiologi,Uppsala Univ, Sweden
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(creator_code:org_t)
- Elsevier, 2024
- 2024
- English.
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In: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 143
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Abstract
Subject headings
Close
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Systemic lupus erythematosus
- Complement system
- Lectin pathway
- Ficolin-3
- Autoantibodies
- Immunologi
- Immunology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lindelöf, Linnea
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Rantapää-Dahlqvi ...
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Lundtoft, Christ ...
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Sandling, Johann ...
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Leonard, Dag, 19 ...
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Sayadi, Ahmed
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Rönnblom, Lars
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Enocsson, Helena
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Sjöwall, Christo ...
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Jönsen, Andreas
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Bengtsson, Ander ...
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Hong, Mun-Gwan, ...
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Diaz-Gallo, Lina ...
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Bianchi, Matteo
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Kozyrev, Sergey ...
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Lindblad-Toh, Ke ...
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Nilsson Ekdahl, ...
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Nilsson, Bo
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Gunnarsson, Iva
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Svenungsson, Eli ...
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Eriksson, Oskar, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
- Articles in the publication
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Journal of Autoi ...
- By the university
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Linnaeus University
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Umeå University
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Stockholm University
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Uppsala University
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Linköping University
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Karolinska Institutet