Factors involved in initiation and regulation of complement lectin pathway influence postoperative outcome after pediatric cardiac surgery involving cardiopulmonary bypass

Abstract

Congenital heart disease (CHD) often requires surgical intervention, and is sometimes associated with life-threatening post-operative complications. We have investigated some factors of the innate immune system involved in the initiation or regulation of complement lectin pathway activation (MASP-1, MASP-2 MASP-3, MAp19, MAp44, ficolin-3) and related them to complications and prognosis in 190 pediatric patients undergoing CHD repair with the use of cardiopulmonary bypass (CPB). Patients with MAp44 levels ≤1.81 µg/ml more frequently experienced low cardiac output syndrome (LCOS), renal insufficiency, systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction (MODS). Low MASP-3 (≤5.18 µg/ml) and high MASP-1 (≥11.7 µg/ml) levels were often associated with fatal outcome. Low ficolin-3 concentrations (≤10.1 µg/ml) were more common among patients experiencing SIRS and MODS than in those without complications. However, patients suffering from SIRS and MODS with low ficolin-3 had a much better prognosis (91% survival vs . 37% among other patients; p = 0.007). A discriminating value of 12.7 µg/ml ficolin-3 yielded 8% vs . 60% mortality (p = 0.001). Our data extend the knowledge concerning involvement of proteins of the lectin pathway in development of post-CPB complications. The potential prognostic value of low preoperative MAp44 and high preoperative ficolin-3 seems promising and warrants independent confirmation.

Serum Proteomics of Older Patients Undergoing Major Cardiac Surgery: Identification of Biomarkers Associated With Postoperative Delirium

“…We noted that cardiac surgery with CPB has been shown to modulate leukocyte recruitment and transmigration ( Rossaint et al, 2012 ), much more than cardiac surgery without CBP ( Tomic et al, 2005 ). Specifically, our findings support a prominent role for ficolin-mediated activation of the lectin pathway of complement during cardiac surgery with CPB, likely in response to damage and pathogen-associated molecular patterns, and CPB circuitry ( Garred et al, 2009 , 2016 ; Michalski et al, 2019 ). In addition to regulating coagulation, ficolins augment inflammatory cytokine release and leukocyte chemotaxis.…”

Associations of ficolins and mannose-binding lectin with acute myeloid leukaemia in adults

“…Therefore, they may prevent certain infections or development of some malignancies via direct lysis of cells expressing pathogen/danger-associated molecular patterns or by enhancement of phagocytosis [12][13][14][15] . On the other hand, complement-activating lectins may be involved in excessive or chronic inflammation which may be harmful to the host, leading in some cases to organ failure or carcinogenesis, respectively [16][17][18] .…”

Association of Polymorphisms of MASP1/3, COLEC10, and COLEC11 Genes with 3MC Syndrome

“…Larsen et al (2019) showed that low MASP-1 concentrations were associated with clotting disorders in patients with septic shock [ 34 ]. Michalski et al (2019) demonstrated that children undergoing surgical correction of congenital heart disease with low pre-operative MAp44 concentration were more likely to suffer from post-operative complications such as systemic inflammatory response syndrome (SIRS), renal failure, multiorgan dysfunction (MODS), or low cardiac output syndrome (LCOS), while high MASP-1 and low MASP-3 were often associated with fatal outcome [ 35 ].…”