RT Journal Article
SR Electronic
T1 The Lectin Pathway of Complement Activation in Patients with Systemic Lupus Erythematosus
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1136
OP 1144
DO 10.3899/jrheum.171033
VO 45
IS 8
A1 Anne Troldborg
A1 Steffen Thiel
A1 Marten Trendelenburg
A1 Justa Friebus-Kardash
A1 Josephine Nehring
A1 Rudi Steffensen
A1 Søren Werner Karlskov Hansen
A1 Magdalena Janina Laska
A1 Bent Deleuran
A1 Jens Christian Jensenius
A1 Anne Voss
A1 Kristian Stengaard-Pedersen
YR 2018
UL http://www.jrheum.org/content/45/8/1136.abstract
AB 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.