Lectin Pathway Enzyme MASP-2 and Downstream Complement Activation in COVID-19
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Lectin Pathway Enzyme MASP-2 and Downstream Complement Activation in COVID-19. / Götz, Maximilian Peter; Skjoedt, Mikkel Ole; Bayarri-Olmos, Rafael; Hansen, Cecilie Bo; Pérez-Alós, Laura; Jarlhelt, Ida; Benfield, Thomas; Rosbjerg, Anne; Garred, Peter.
In: Journal of Innate Immunity, Vol. 15, No. 1, 2023, p. 122–135.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Lectin Pathway Enzyme MASP-2 and Downstream Complement Activation in COVID-19
AU - Götz, Maximilian Peter
AU - Skjoedt, Mikkel Ole
AU - Bayarri-Olmos, Rafael
AU - Hansen, Cecilie Bo
AU - Pérez-Alós, Laura
AU - Jarlhelt, Ida
AU - Benfield, Thomas
AU - Rosbjerg, Anne
AU - Garred, Peter
N1 - Publisher Copyright: © 2022
PY - 2023
Y1 - 2023
N2 - Mannose-binding lectin-associated serine protease 2 (MASP-2) is the main activator of the lectin complement pathway and has been suggested to be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). To study a possible association between MASP-2 and COVID-19, we aimed at developing a sensitive and reliable MASP-2 ELISA. From an array of novel mouse-monoclonal antibodies using recombinant MASP-2 as antigen, two clones were selected to create a sandwich ELISA. Plasma samples were obtained from 216 healthy controls, 347 convalescent COVID-19 patients, and 147 prospectively followed COVID-19 patients. The assay was specific towards MASP-2 and did not recognize the truncated MASP2 splice variant MAP-2 (MAp19). The limit of quantification was shown to be 0.1 ng/mL. MASP-2 concentration was found to be stable after multiple freeze-thaw cycles. In healthy controls, the mean MASP-2 concentration was 524 ng/mL (95% CI: 496.5-551.6). No significant difference was found in the MASP-2 concentrations between COVID-19 convalescent samples and controls. However, a significant increase was observed in prospectively followed COVID-19 patients (mean: 834 ng/mL [95% CI: 765.3-902.7, p < 0.0001]). In these patients, MASP-2 concentration correlated significantly with the concentrations of the terminal complement complex (ρ = 0.3596, p < 0.0001), with the lectin pathway pattern recognition molecules ficolin-2 (ρ = 0.2906, p = 0.0004) and ficolin-3 (ρ = 0.3952, p < 0.0001) and with C-reactive protein (ρ = 0.3292, p = 0.0002). Overall, we developed a specific quantitative MASP-2 sandwich ELISA. MASP-2 correlated with complement activation and inflammatory markers in COVID-19 patients, underscoring a possible role of MASP-2 in COVID-19 pathophysiology.
AB - Mannose-binding lectin-associated serine protease 2 (MASP-2) is the main activator of the lectin complement pathway and has been suggested to be involved in the pathophysiology of coronavirus disease 2019 (COVID-19). To study a possible association between MASP-2 and COVID-19, we aimed at developing a sensitive and reliable MASP-2 ELISA. From an array of novel mouse-monoclonal antibodies using recombinant MASP-2 as antigen, two clones were selected to create a sandwich ELISA. Plasma samples were obtained from 216 healthy controls, 347 convalescent COVID-19 patients, and 147 prospectively followed COVID-19 patients. The assay was specific towards MASP-2 and did not recognize the truncated MASP2 splice variant MAP-2 (MAp19). The limit of quantification was shown to be 0.1 ng/mL. MASP-2 concentration was found to be stable after multiple freeze-thaw cycles. In healthy controls, the mean MASP-2 concentration was 524 ng/mL (95% CI: 496.5-551.6). No significant difference was found in the MASP-2 concentrations between COVID-19 convalescent samples and controls. However, a significant increase was observed in prospectively followed COVID-19 patients (mean: 834 ng/mL [95% CI: 765.3-902.7, p < 0.0001]). In these patients, MASP-2 concentration correlated significantly with the concentrations of the terminal complement complex (ρ = 0.3596, p < 0.0001), with the lectin pathway pattern recognition molecules ficolin-2 (ρ = 0.2906, p = 0.0004) and ficolin-3 (ρ = 0.3952, p < 0.0001) and with C-reactive protein (ρ = 0.3292, p = 0.0002). Overall, we developed a specific quantitative MASP-2 sandwich ELISA. MASP-2 correlated with complement activation and inflammatory markers in COVID-19 patients, underscoring a possible role of MASP-2 in COVID-19 pathophysiology.
KW - Assay
KW - COVID-19
KW - Inflammation
KW - Mannose-binding lectin-associated serine protease 2
KW - MASP-2
KW - Outcome
U2 - 10.1159/000525508
DO - 10.1159/000525508
M3 - Journal article
C2 - 35816998
AN - SCOPUS:85135195674
VL - 15
SP - 122
EP - 135
JO - Journal of Innate Immunity
JF - Journal of Innate Immunity
SN - 1662-811X
IS - 1
ER -
ID: 319161543