MASP2 levels are elevated in thrombotic microangiopathies: association with microvascular endothelial cell injury and suppression by anti-MASP2 antibody narsoplimab.

Clinical and Experimental Immunology
S ElhadadJ Laurence

Abstract

Involvement of the alternative complement pathway (AP) in microvascular endothelial cell (MVEC) injury characteristic of a thrombotic microangiopathy (TMA) is well documented. However, the role of the lectin pathway (LP) of complement has not been explored. We examined mannose-binding lectin associated serine protease (MASP2), the effector enzyme of the LP, in thrombotic thrombocytopenic purpura, atypical hemolytic uremic syndrome and post-allogeneic hematopoietic stem cell transplantation (alloHSCT) TMAs. Plasma MASP2 and terminal complement component sC5b-9 levels were assessed by enzyme-linked immunosorbent assay (ELISA). Human MVEC were exposed to patient plasmas, and the effect of the anti-MASP2 human monoclonal antibody narsoplimab on plasma-induced MVEC activation was assessed by caspase 8 activity. MASP2 levels were highly elevated in all TMA patients versus controls. The relatively lower MASP2 levels in alloHSCT patients with TMAs compared to levels in alloHSCT patients who did not develop a TMA, and a significant decrease in variance of MASP2 levels in the former, may reflect MASP2 consumption at sites of disease activity. Plasmas from 14 of the 22 TMA patients tested (64%) induced significant MVEC caspase 8 activatio...Continue Reading

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Citations

Jan 19, 2021·MAbs·Hélène Kaplon, Janice M Reichert
Jan 29, 2021·Frontiers in Immunology·Chiara AgostinisRoberta Bulla
Apr 2, 2021·Journal of Blood Medicine·Christos VarelasEfthymia Vlachaki
Apr 4, 2021·Medical Microbiology and Immunology·Qin Li, Zi Chen
Jun 3, 2021·Journal of Clinical Medicine·Nicole Ng, Charles A Powell
Jul 1, 2021·Seminars in Immunopathology·M JalinkI Jongerius
Sep 18, 2021·Current Opinion in Hematology·Michelle SchoettlerLeslie Lehmann

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Methods Mentioned

BETA
biopsy
enzyme‐linked immunosorbent assays
fluorescence resonance

Clinical Trials Mentioned

NCT02604420

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