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Lectin Pathway Enzyme MASP-2 and Downstream Complement Activation in COVID-19.
Maximilian Peter Götz1, Mikkel-Ole Skjoedt2,3, Rafael Bayarri-Olmos2
1Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark, maximilianpetergoetz@gmail.com.
Journal of Innate Immunity
|July 11, 2022
Summary
Mannose-binding lectin-associated serine protease 2 (MASP-2) levels increase in active COVID-19 patients, correlating with complement activation and inflammation. This suggests MASP-2 plays a role in COVID-19 pathophysiology, aiding in disease understanding.
Area of Science:
- Immunology
- Complement System
- Virology
Background:
- Mannose-binding lectin-associated serine protease 2 (MASP-2) activates the lectin complement pathway.
- MASP-2 involvement in COVID-19 pathophysiology is hypothesized.
- A sensitive and reliable assay for MASP-2 is needed.
Purpose of the Study:
- To develop a specific and quantitative MASP-2 enzyme-linked immunosorbent assay (ELISA).
- To investigate MASP-2 concentrations in healthy controls and COVID-19 patients.
- To explore the correlation between MASP-2 and complement activation/inflammatory markers in COVID-19.
Main Methods:
- Development of a sandwich ELISA using novel mouse monoclonal antibodies against MASP-2.
- Assay validation for specificity, limit of quantification (0.1 ng/mL), and stability.
- Measurement of MASP-2 concentrations in plasma from 216 healthy controls, 347 convalescent COVID-19 patients, and 147 prospectively followed COVID-19 patients.
Main Results:
- The developed ELISA specifically detected MASP-2 and not its splice variant MAP-2.
- MASP-2 concentrations were stable after freeze-thaw cycles.
- Healthy controls had a mean MASP-2 of 524 ng/mL.
- No significant difference in MASP-2 was found in convalescent COVID-19 patients compared to controls.
- Prospectively followed COVID-19 patients showed a significant increase in MASP-2 (mean 834 ng/mL, p < 0.0001).
- In active COVID-19 patients, MASP-2 correlated with terminal complement complex, ficolins (ficolin-2, ficolin-3), and C-reactive protein.
Conclusions:
- A specific and quantitative MASP-2 ELISA was successfully developed.
- Elevated MASP-2 levels in active COVID-19 patients correlate with complement activation and inflammation.
- These findings support a potential role for MASP-2 in the pathophysiology of COVID-19.
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