Lectin Pathway Enzyme MASP-2 and Downstream Complement Activation in COVID-19

Maximilian Peter Götz, Mikkel Ole Skjoedt, Rafael Bayarri-Olmos, Cecilie Bo Hansen, Laura Pérez-Alós, Ida Jarlhelt, Thomas Benfield, Anne Rosbjerg, Peter Garred*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

8 Citationer (Scopus)
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Abstract

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.

OriginalsprogEngelsk
TidsskriftJournal of Innate Immunity
Vol/bind15
Udgave nummer1
Sider (fra-til)122–135
ISSN1662-811X
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was supported by funds provided to Peter Garred by the EU HORIZON 2020 MSCA ITN project CORVOS 860044.

Publisher Copyright:
© 2022

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