Mannose Binding Lectin, S100 B Protein, and Brain Injuries in Neonates With Perinatal Asphyxia.

Cinzia Auriti,Tamara Del Pinto,Maria Moriondo,Rita Inglese,Silvia Bucci,Daniela Longo,Laura Timelli,Vito Mondì,Francesco Nieddu,Giusi Prencipe,Vincenzo Maria Di Ciommo

doi:10.3389/fped.2020.00527

Abstract

Perinatal asphyxia triggers an acute inflammatory response in the injured brain. Complement activation and neuroinflammation worsen brain damage after a systemic ischemia/reperfusion insult. The increase of mannose binding lectin (MBL) during asphyxia may contribute to the brain damage, via activation of the complement lectin pathway. The possible role of MBL2 gene variants in influencing the severity of post-asphyxia brain injuries is still unexplored. This retrospective study included 53 asphyxiated neonates: 42 underwent therapeutic hypothermia (TH) and 11 did not because they were admitted to the NICU later than 6 h after the hypoxic insult. Blood samples from TH-treated and untreated patients were genotyped for MBL2 gene variants, and biomarker plasma levels (MBL and S100 B protein) were measured at different time points: during hypothermia, during rewarming, and at 7–10 days of life. The timing of blood sampling, except for the T1 sample, was the same in untreated infants. Highest (peak) levels of MBL and MBL2 genotypes were correlated to neuroimaging brain damage or death and long-term neurodevelopmental delay. MBL2 wild-type genotype was associated with the highest MBL levels and worst brain damage on MRI (p = 0.046) at 7–10 days after hypoxia. MBL increased in both groups and S100B decreased, slightly more in treated than in untreated neonates. The progressive increase of MBL (p = 0.08) and to be untreated with TH (p = 0.08) increased the risk of brain damage or death at 7–10 days of life, without affecting neurodevelopmental outcomes at 1 year. The effect of TH on MBL plasma profiles is uncertain.

Highlights

Perinatal asphyxia triggers an acute inflammatory response in the injured brain
We evaluated the effect of therapeutic hypothermia (TH) on plasma levels of Mannose binding lectin (MBL) and S100B protein in these patients
The two groups differed in age at admission, intubation before admission to the neonatal intensive care unit (NICU), and Sarnat score at birth, with all of the data indicating that neonates treated with HT presented with a more serious clinical condition compared with the untreated neonates

Summary

Introduction

Perinatal asphyxia triggers an acute inflammatory response in the injured brain. Many studies [1,2,3,4] report an increase in circulating cytokine and chemokine levels in neonates with hypoxic ischemic encephalopathy, highlighting the role of neuroinflammation in brain damage. MBL has many important functions: it has opsonic and inflammatory actions, stimulates macrophage activation, facilitates phagocytosis, and promotes the lectin pathway of the complement system [7,8,9]. Circulating MBL, like other acute phase proteins, increases in neonates during the first weeks of life [10], and low plasma MBL levels appear to increase the risk of infection in preterm and full-term neonates [11,12,13,14]. The wild-type genotype promotes a robust inflammatory response and high plasma MBL levels after infectious and inflammatory stimuli. Mutations in both the promoter and exon-1 domains of MBL2, which affect ∼20% of the Caucasian population, cause quantitative, and functional deficiency of circulating MBL in response to the same infectious and inflammatory stimuli. MBL appears to have other functions in addition to protecting against infections and debate continues as to the clinical relevance of low or high MBL levels in these subjects [15,16,17,18]

Methods

Results

Conclusion