Increased incidence and severity of the systemic inflammatory response syndrome in patients deficient in mannose-binding lectin.
OBJECTIVE
To determine whether pediatric PICU patients with mannose-binding lectin (MBL) gene polymorphisms associated with low levels of the functional protein have an increased risk of developing sepsis and SIRS.


METHODS
A prospective, observational cohort study in a 22-bed PICU in a tertiary referral centre.


METHODS
One hundred consecutive admissions to a PICU with at least one organ system failure longer than 12 h. Patients were classified into those with infectious or non-infectious insults as the primary reason for intensive care admission. Patients were followed to determine which developed sepsis or non-infection related SIRS using standard criteria.


RESULTS
Of the 100 patients 50 had infectious and 50 had non-infectious insults as the precipitant for admission. 42 patients had variant MBL alleles (determined by MBL-2 gene exon 1 and promoter polymorphisms) and were significantly over-represented amongst the 59 patients that developed SIRS. This effect was not explained by differences in age, sex or ethnicity and was seen in both the infection and non-infection subgroups. In patients with infection, variant MBL alleles were associated with increased systemic response (2/15 with localised infection, 10/19 with sepsis and 12/16 with septic shock). MBL serum levels showed close concordance with the genotype and indicated that MBL levels less than 1000 ng/ml are associated with a greatly increased risk of SIRS.


CONCLUSIONS
MBL-2 exon 1 polymorphisms with low serum levels of functional MBL protein are associated with a greatly increased risk of developing SIRS and of progression from infection to sepsis and septic shock in paediatric ICU patients.
Fidler
Katy J
KJ
Infectious Diseases and Microbiology Unit, Institute of Child Health, 30 Guilford Street, London, WC1 N 1EH, UK.
Wilson
Peter
P
Davies
Jane C
JC
Turner
Malcolm W
MW
Peters
Mark J
MJ
Klein
Nigel J
NJ
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D007223:Infant; D015278:Intensive Care Units, Pediatric; D008297:Male; D037601:Mannose-Binding Lectin / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006113:United Kingdom / Q000453:epidemiology
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin