TY - JOUR
T1 - The Lectin Pathway of Complement Activation in Patients with Systemic Lupus Erythematosus
AU - Troldborg, Anne
AU - Thiel, Steffen
AU - Trendelenburg, Marten
AU - Friebus-Kardash, Justa
AU - Nehring, Josephine
AU - Steffensen, Rudi
AU - Hansen, Søren Werner Karlskov
AU - Laska, Magdalena Janina
AU - Deleuran, Bent
AU - Jensenius, Jens Christian
AU - Voss, Anne
AU - Stengaard-Pedersen, Kristian
PY - 2018
Y1 - 2018
N2 - 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.
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.
KW - Complement activation
KW - Complement system
KW - Innate immunity
KW - Lectin pathway
KW - Systemic lupus erythematosus
UR - http://www.scopus.com/inward/record.url?scp=85051705047&partnerID=8YFLogxK
U2 - 10.3899/jrheum.171033
DO - 10.3899/jrheum.171033
M3 - Journal article
C2 - 29907670
SN - 0315-162X
VL - 45
SP - 1136
EP - 1144
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 8
ER -