Anne Troldborg1,2, Steffen Thiel3,4, Marten Trendelenburg3,4, Justa Friebus-Kardash3,4, Josephine Nehring3,4, Rudi Steffensen3,4, Søren Werner Karlskov Hansen3,4, Magdalena Janina Laska3,4, Bent Deleuran3,4, Jens Christian Jensenius3,4, Anne Voss3,4, Kristian Stengaard-Pedersen3,4. 1. From the Department of Rheumatology, Aarhus University Hospital; Institute of Clinical Medicine, and Department of Biomedicine, Aarhus University, Aarhus; Department of Clinical Immunology, Aalborg University Hospital, Aalborg; Department of Cancer and Inflammation Research, University of Southern Denmark; Department of Rheumatology, Odense University Hospital, Odense, Denmark; Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. annetrol@rm.dk. 2. A. Troldborg, MD, PhD, Department of Rheumatology, Aarhus University Hospital, and Institute of Clinical Medicine, Aarhus University; S. Thiel, PhD, Professor, Department of Biomedicine, Aarhus University; M. Trendelenburg, PhD, Professor, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; J. Friebus-Kardash, MD, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; J. Nehring, MD, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; R. Steffensen, PhD, Department of Clinical Immunology, Aalborg University Hospital; S.W. Hansen, PhD, Associate Professor, Department of Cancer and Inflammation Research, University of Southern Denmark; M.J. Laska, PhD, Associate Professor, Institute of Clinical Medicine, Aarhus University, and Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; B. Deleuran, PhD, Professor, Department of Rheumatology, Aarhus University Hospital, and Department of Biomedicine, Aarhus University; J.C. Jensenius, PhD, Professor, Department of Biomedicine, Aarhus University; A. Voss, MD, PhD, Department of Rheumatology, Odense University Hospital; K. Stengaard-Pedersen, PhD, Professor, Department of Rheumatology, Aarhus University Hospital, and Institute of Clinical Medicine, Aarhus University. annetrol@rm.dk. 3. From the Department of Rheumatology, Aarhus University Hospital; Institute of Clinical Medicine, and Department of Biomedicine, Aarhus University, Aarhus; Department of Clinical Immunology, Aalborg University Hospital, Aalborg; Department of Cancer and Inflammation Research, University of Southern Denmark; Department of Rheumatology, Odense University Hospital, Odense, Denmark; Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland. 4. A. Troldborg, MD, PhD, Department of Rheumatology, Aarhus University Hospital, and Institute of Clinical Medicine, Aarhus University; S. Thiel, PhD, Professor, Department of Biomedicine, Aarhus University; M. Trendelenburg, PhD, Professor, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; J. Friebus-Kardash, MD, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; J. Nehring, MD, Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; R. Steffensen, PhD, Department of Clinical Immunology, Aalborg University Hospital; S.W. Hansen, PhD, Associate Professor, Department of Cancer and Inflammation Research, University of Southern Denmark; M.J. Laska, PhD, Associate Professor, Institute of Clinical Medicine, Aarhus University, and Division of Internal Medicine and Department of Biomedicine, University Hospital Basel, University of Basel; B. Deleuran, PhD, Professor, Department of Rheumatology, Aarhus University Hospital, and Department of Biomedicine, Aarhus University; J.C. Jensenius, PhD, Professor, Department of Biomedicine, Aarhus University; A. Voss, MD, PhD, Department of Rheumatology, Odense University Hospital; K. Stengaard-Pedersen, PhD, Professor, Department of Rheumatology, Aarhus University Hospital, and Institute of Clinical Medicine, Aarhus University.
Abstract
OBJECTIVE: The pathogenesis of systemic lupus erythematosus (SLE) involves complement activation. Activation of complement through the classical pathway (CP) is well established. However, complement activation through pattern recognition not only happens through the CP, but also through the lectin pathway (LP). We investigated the hypothesis that the LP is activated in SLE and involved in the pathogenesis of the disease. METHODS: Using immunoassays developed in-house, we measured concentrations of LP proteins in a cohort of 372 patients with SLE and 170 controls. We estimated complement activation measuring total C3, and investigated whether LP protein concentrations were associated with complement activation and disease activity. Protein changes and disease activity over time were assessed in a cohort of 52 patients with SLE followed with repeated samples over a 5-year period. RESULTS: Concentrations of LP proteins in SLE were altered compared with controls. The differences observed in LP proteins associated with complement activation were reflected by a decrease in total C3. The pattern recognition molecules (M-ficolin, CL-L1, and CL-K1), the serine protease (MASP-3), and the associated protein (MAp19) displayed a negative correlation with disease activity. Changes in MASP-2 concentrations over time correlated significantly with increased disease activity. Association between active proteinuria and serum concentration was observed for MASP-3 and MAp19. CONCLUSION: In patients with SLE, we measured specific changes in LP proteins that are associated with complement activation and disease activity, indicating that the LP is activated in patients with SLE. These novel findings substantiate the involvement of the LP in SLE.
OBJECTIVE: The pathogenesis of systemic lupus erythematosus (SLE) involves complement activation. Activation of complement through the classical pathway (CP) is well established. However, complement activation through pattern recognition not only happens through the CP, but also through the lectin pathway (LP). We investigated the hypothesis that the LP is activated in SLE and involved in the pathogenesis of the disease. METHODS: Using immunoassays developed in-house, we measured concentrations of LP proteins in a cohort of 372 patients with SLE and 170 controls. We estimated complement activation measuring total C3, and investigated whether LP protein concentrations were associated with complement activation and disease activity. Protein changes and disease activity over time were assessed in a cohort of 52 patients with SLE followed with repeated samples over a 5-year period. RESULTS: Concentrations of LP proteins in SLE were altered compared with controls. The differences observed in LP proteins associated with complement activation were reflected by a decrease in total C3. The pattern recognition molecules (M-ficolin, CL-L1, and CL-K1), the serine protease (MASP-3), and the associated protein (MAp19) displayed a negative correlation with disease activity. Changes in MASP-2 concentrations over time correlated significantly with increased disease activity. Association between active proteinuria and serum concentration was observed for MASP-3 and MAp19. CONCLUSION: In patients with SLE, we measured specific changes in LP proteins that are associated with complement activation and disease activity, indicating that the LP is activated in patients with SLE. These novel findings substantiate the involvement of the LP in SLE.
Authors: Anne Troldborg; Rudi Steffensen; Marten Trendelenburg; Thomas Hauser; Kasper G Winther; Annette G Hansen; Kristian Stengaard-Pedersen; Anne Voss; Steffen Thiel Journal: J Clin Immunol Date: 2019-05-01 Impact factor: 8.317
Authors: A Troldborg; S Thiel; C E Mistegaard; A Hansen; T-L Korsholm; K Stengaard-Pedersen; A G Loft Journal: Clin Exp Immunol Date: 2019-10-01 Impact factor: 4.330
Authors: Na Wang; Weiju Wu; Cui Qiang; Ning Ma; Kunyi Wu; Dan Liu; Jia-Xing Wang; Xiao Yang; Li Xue; Teng-Yue Diao; Jia-Yu Liu; Ang Li; Baojun Zhang; Zong-Fang Li; Conrad A Farrar; Nirmal K Banda; Rafael Bayarri-Olmos; Peter Garred; Wuding Zhou; Ke Li Journal: Arthritis Rheumatol Date: 2021-07-07 Impact factor: 15.483
Authors: Kristian Juul-Madsen; Anne Troldborg; Thomas R Wittenborn; Mads G Axelsen; Huaying Zhao; Lasse H Klausen; Stefanie Luecke; Søren R Paludan; Kristian Stengaard-Pedersen; Mingdong Dong; Holger J Møller; Steffen Thiel; Henrik Jensen; Peter Schuck; Duncan S Sutherland; Søren E Degn; Thomas Vorup-Jensen Journal: Proc Natl Acad Sci U S A Date: 2021-07-27 Impact factor: 11.205
Authors: Mia Glerup; Steffen Thiel; Veronika Rypdal; Ellen Dalen Arnstad; Maria Ekelund; Suvi Peltoniemi; Kristiina Aalto; Marite Rygg; Susan Nielsen; Anders Fasth; Lillemor Berntson; Ellen Nordal; Troels Herlin Journal: Pediatr Rheumatol Online J Date: 2019-09-09 Impact factor: 3.054