Anne Troldborg1,2,3, Rudi Steffensen4, Marten Trendelenburg5, Thomas Hauser6, Kasper G Winther7, Annette G Hansen7, Kristian Stengaard-Pedersen8, Anne Voss9, Steffen Thiel7. 1. Department of Rheumatology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark. annetrol@rm.dk. 2. Department of Biomedicine, Aarhus University, Aarhus, Denmark. annetrol@rm.dk. 3. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. annetrol@rm.dk. 4. Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. 5. Division of Internal Medicine and Clinical Immunology lab, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. 6. IZZ Immunologie-Zentrum Zürich, Zürich, Switzerland. 7. Department of Biomedicine, Aarhus University, Aarhus, Denmark. 8. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 9. Department of Rheumatology, Odense University Hospital, Odense, Denmark.
Abstract
PURPOSE: Ficolin-3 deficiency is caused by a mutation (+1637delC) in the FCN3 gene. It is a rare condition and has been associated with both infection and autoimmune disease including systemic lupus erythematosus (SLE). Here we investigated if ficolin-3 deficiency is more frequent in patients than in controls and tried to identify a common phenotype among ficolin-3 deficient individuals. Since a significant part of patients identified with ficolin-3 deficiency was diagnosed with SLE, we explored whether the heterozygous state of the FCN3+1637delC variant represents a risk factor in the development of SLE. Further, we examined other possible causes of ficolin-3 deficiency when the FCN3+1637delC is not present. METHODS: A systematic literature search for studies measuring ficolin-3 was carried out. We examined 362 SLE patients and 596 controls for the presence of the variant FCN3+1637delC. We established assays for measurements of ficolin-3 and of auto-antibodies against ficolin-3. We sequenced the coding and non-coding regions of the FCN3 gene in an SLE patient with ficolin-3 deficiency not carrying the +1637delC. RESULTS: Ficolin-3 deficiency leads to an 8-time increased odds of having a disease (p < 0.05). Three out of nine patients with deficiency had SLE. The heterozygous state of the deficiency variant is not associated with increased risk of developing SLE (p = 0.18). CONCLUSION: By systematically reviewing the literature for the described cases of ficolin-3 deficiency, an autoimmune phenotype is emerging. Thirty-three percent of the ficolin-3 deficient patients had SLE. Heterozygosity for the FCN3 gene deletion causing the deficiency does not seem to be associated with the development of SLE.
PURPOSE:Ficolin-3 deficiency is caused by a mutation (+1637delC) in the FCN3 gene. It is a rare condition and has been associated with both infection and autoimmune disease including systemic lupus erythematosus (SLE). Here we investigated if ficolin-3 deficiency is more frequent in patients than in controls and tried to identify a common phenotype among ficolin-3 deficient individuals. Since a significant part of patients identified with ficolin-3 deficiency was diagnosed with SLE, we explored whether the heterozygous state of the FCN3+1637delC variant represents a risk factor in the development of SLE. Further, we examined other possible causes of ficolin-3 deficiency when the FCN3+1637delC is not present. METHODS: A systematic literature search for studies measuring ficolin-3 was carried out. We examined 362 SLEpatients and 596 controls for the presence of the variant FCN3+1637delC. We established assays for measurements of ficolin-3 and of auto-antibodies against ficolin-3. We sequenced the coding and non-coding regions of the FCN3 gene in an SLEpatient with ficolin-3 deficiency not carrying the +1637delC. RESULTS:Ficolin-3 deficiency leads to an 8-time increased odds of having a disease (p < 0.05). Three out of nine patients with deficiency had SLE. The heterozygous state of the deficiency variant is not associated with increased risk of developing SLE (p = 0.18). CONCLUSION: By systematically reviewing the literature for the described cases of ficolin-3 deficiency, an autoimmune phenotype is emerging. Thirty-three percent of the ficolin-3 deficient patients had SLE. Heterozygosity for the FCN3 gene deletion causing the deficiency does not seem to be associated with the development of SLE.
Authors: Luis E Muñoz; Kirsten Lauber; Martin Schiller; Angelo A Manfredi; Martin Herrmann Journal: Nat Rev Rheumatol Date: 2010-05 Impact factor: 20.543
Authors: Lea Munthe-Fog; Tina Hummelshøj; Christian Honoré; Hans O Madsen; Henrik Permin; Peter Garred Journal: N Engl J Med Date: 2009-06-18 Impact factor: 91.245
Authors: Tom Sprong; Tom Eirik Mollnes; Chris Neeleman; Dorine Swinkels; Mihai G Netea; Jos W M van der Meer; Marcel van Deuren Journal: Clin Infect Dis Date: 2009-11-01 Impact factor: 9.079
Authors: Lea Munthe-Fog; Tina Hummelshøj; Ying Jie Ma; Bjarke E Hansen; Claus Koch; Hans O Madsen; Karsten Skjødt; Peter Garred Journal: Mol Immunol Date: 2008-02-07 Impact factor: 4.407
Authors: M Isabel García-Laorden; Elisa Hernández-Brito; Carmen Muñoz-Almagro; Svetlana Pavlovic-Nesic; Iñigo Rúa-Figueroa; M Luisa Briones; Olga Rajas; Luis Borderías; Antoni Payeras; Leonardo Lorente; Jordi Freixinet; Jose Ferreres; Ignacio Obando; Nereida González-Quevedo; Felipe Rodríguez de Castro; Jordi Solé-Violán; Carlos Rodríguez-Gallego Journal: J Clin Immunol Date: 2019-12-11 Impact factor: 8.317