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Genetic polymorphisms of innate immunity and susceptibility to pneumococcal infection

Abstract number: P2078

García-Cabrera E., Garnacho-Montero J., Jiménez-Alvarez R., Revuleto-Rey J., Diaz-Martin A., García-Curiel A., Barroso S., Aznar-Martin J., Ortiz-Leyba C.

Objective: To investigate whether diverse genetic variants of innate immunity (MBL, TLR2, TLR4, and FcgRIIa) that cause hyporesponsiveness to S. pneumoniae might be associated with a higher risk of invasive pneumococcal disease in adults.

Methods: All adult patients with community-acquired Streptococcus pneumoniae disease admitted to the hospital from January 2005 to November 2007 were enrolled in this prospective study. Patients with congenital immunodeficiencies, HIV infections and severe neutropenia (<500 cells/mm3) were excluded from this protocol. Controls were patients of the same hospitalisation area and similar age range with negative blood culture and without previous history of pneumonia or meningitis. After obtaining written consent, we performed genotype analysis with 5 ml of peripheral blood and extract the DNA with (High Pure PCR Template Preparation Kit, Roche). By PCR-RFLP were detected MBL allelic variant B (ID:rs1800450), C (rs1800451) and TLR2 Arg753Gln (rs5743708). The MBL D variant (rs5030737), and Arg131His FcgRIIa, were performed by PCR. TLR4 Asp299Gly (rs4986790) was determined by sequencing the specific region. For statistical analysis, categorical variables were analysed using the chi-square test and Fisher's test when appropriate. Continuous variables were compared using the Mann-Whitney U. Significant differences were defined as p < 0.05.

Results: One hundred and eighteen patients were included; of them, 75 patients (63.5%) were bacteraemic. The source of the pneumococcal disease were pneumonia 98 (83.1%), meningitis 18 (15.3%) and abdominal focus 2 (1.7%). Of them, 74 patients (62.7%) were admitted to the ICU, and 40 patients (34.2%) developed septic shock. The mortality rate was 18.8% (22 patients). The median age of the patients was 60 years±23 IQR and the median age of the controls (n = 52) was 55 years±28 IQR (p = 0.213). TLR4 Asp299Gly polymorphism was present in 25.4% of patients with pneumococcal disease and in 0% of control subjects (p < 0.001). In addiction, TLR2 Arg753Gln polymorphism was present in 5.6% of patients with pneumococcal disease and in 0% of control subjects (p = 0.156). Frequency of the other variant alleles was similar in infected patients and controls.

Conclusions: Among the assessed genetic variants of innate immunity, only TLR4 Asp299Gly polymorphism is associated with a higher risk of invasive pneumococcal infection in adults.

Session Details

Date: 16/05/2009
Time: 00:00-00:00
Session name: 19th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Helsinki, Finland, 16 - 19 May 2009
Presentation type:
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