Interleukin 1 receptor antagonist (IL1RA) gene polymorphism and levels associated with adverse outcome in severe community-acquired pneumonia in children: A hospital-based study in India

Abstract

Background: High morbidity and mortality due to community-acquired pneumonia (CAP) is seen in children under 5 years of age in India. Besides identified risk factors for CAP, there may be a phenotype-genotype association with cytokines, resulting in enhanced inflammatory response resulting in the adverse outcome (AO), namely complications and death.

Aim: To assess the association of IL1RA gene polymorphism on serum levels of IL1RA and with AO in children under 5 years of age hospitalized with WHO-defined severe CAP.

Method: A prospective cohort study with nested case-control design conducted in a tertiary care teaching hospital after obtaining institutional ethical approval. Included were children between 2 and 59 months of age hospitalized with WHO-defined severe CAP with consistent radiological abnormalities. Excluded were those with suspected or proven cystic fibrosis, pulmonary tuberculosis, malignancy, immunodeficiency, and congenital heart disease. Polymerase chain reaction (PCR) was used to analyze the Variable Number of Tandem Repeats (VNTRs) of IL1RA gene polymorphism and ELISA test to detect serum levels of IL1RA.

Results: From 2014 to 2016, of 420 screened cases, 350 were eligible and included, of which 132 (37.7%) had no complication and 218 (62.3%) had AO, which included complications like empyema, pyopneumothorax, acute respiratory distress syndrome (ARDS), and septic shock of these 24 (6.9%) expired. Higher risk of AO was seen in A2A2 genotype (OR 11.18, p 0.0001) and lower in A1A1 genotype (OR 0.18, P < 0.0001). Serum IL1RA (ng/mL) was statistically significantly elevated in CAP with AO (2.55 ± 1.44) versus uncomplicated (0.87 ± 0.52) (P < 0.0001).

Conclusion: In IL1RA gene, A1A1 genotype was associated with lower risk and A2A2 genotype with increased the risk of AO. Higher serum levels of IL1RA were found in A2A2 genotype indicating possibly enhanced inflammatory response resulting in AO of CAP.

Keywords: IL1RA serum levels; India; Interleukin 1 receptor antagonist (IL1 RA) gene polymorphisms; children; community-acquired pneumonia.