Infection and sepsis in severely injured patients is associated with single nucleotide polymorphisms in MBL2, MASP2 and FCN2 within the lectin pathway

Background. Infectious complications remain a serious threat to polytraumatized patients. Susceptibility and response to infection is, in part, heritable. The lectin pathway plays a major role in innate immunity. The aim of this study was to assess if single nucleotide polymorphisms (SNPs) in three key genes within the lectin pathway affect susceptibility to infectious complications in severely injured patients. Methods. A prospective cohort of trauma patients admitted to a Level I Trauma Center between January 2008 and April 2011 was genotyped for SNPs in MBL2 (Mannose-Binding Lectin 2), MASP2 (MBL-Associated Serine Protease 2), and FCN2 (Ficolin 2). Association of genotype with prevalence of infection was tested with chi-square and logistic regression analysis. Results. A total of 219 patients were included, of which 112 (51%) developed a positive culture in either sputum, wounds, blood, or urine. Systemic Inflammatory Response Syndrome (SIRS) developed in 140 patients ( 64%), sepsis in 79 (36%), and septic shock in 37 (17%). Patients with a MBL2 exon 1 variant allele were more prone to positive wound cultures (OR 2.50, p=0.025). A MASP2 Y371D DD genotype predisposed for SIRS (OR 4.78; p=0.042) and septic shock (OR 2.53; p=0.003). A FCN2 A258S AS genotype predisposed for positive wound cultures (OR 3.37; p=0.005) and septic shock (OR 2.18 p=0.011). Conclusion. Severely injured patients with SNPs in MBL2, MASP2 Y371D and FCN2 A258S of the lectin pathway of complement activation are significantly more susceptible to positive culture findings and to infectious complications, SIRS and septic shock than patients with a common (wildtype) genotype.