Assessment of Toll Like receptor 2 Gene Polymorphism in Children with B Cell Defects and Respiratory Tract Infections

Abstract

Abstract Acute respiratory tract infections are the most common illnesses in childhood. Respiratory defenses against infection involve a diverse and complex system. Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs), recognize pathogen-associated molecular patterns (PAMPs), resulting in initiation of innate immune response and promotion of adaptive immunity. TLR single nucleotide polymorphisms (SNPs) impair the ability to respond properly to TLR ligands and increase susceptibility to infectious or inflammatory diseases. The aim of the work: To examine TLR2 Arginine 677Tryptophan (Arg 677Trp) and Arginine753Glutamine (Arg753Gln) gene polymorphisms in patients with recurrent or chronic respiratory tract infections with or without predominantly antibody deficiency (PAD). Subjects and methods: This cross-sectional case-control study included 30 patients with known PAD with/ or without respiratory tract infections, 20 non-PAD patients with recurrent chest infections and 20 age and sex-matched healthy controls. All children included in the study were subjected to full history taking, complete physical examination and laboratory investigations including CBC, serum immunoglobulins levels and genetic analysis of the TLR2 Arg677Trp and Arg753Gln polymorphisms. Computed tomography (CT) scan of the chest with contrast, pulmonary function tests (PFTs) and Bronchoalveolar lavage (BAL) fluid culture and sensitivity were performed to patients with recurrent and/or chronic chest infections. Results: There was a significant difference in the expression of Arg753Gln polymorphism (p 0.04) between PAD patients with and without recurrent chest infections. Patients with mutant or heterozygote state of this polymorphism had a short diagnosis lag (time elapsed between onset of symptoms and date of diagnosis). There was a significant relationship between this polymorphism and the duration of hospital admission (longer hospital stay in patients with mutant allele). A significant difference between non-PAD patients with recurrent chest infections and healthy controls regarding Arg 677 Trp polymorphism (p 0.04) was elicited. Conclusion: Our results suggest that Arg 677 Trp polymorphism could be a risk factor for increased susceptibility to recurrent and /or chronic respiratory tract infections in patients without PAD, while Arg753Gln polymorphism might be an additional risk factor for severe infections in PAD patients.