Immunoglobulin heavy G2 chain (IGHG2) gene restriction in the development of severe respiratory syncytial virus infection

Aim: Respiratory syncytial virus (RSV) is a prominent cause of airway morbidity in children under 1 y of age. It is assumed that host factors influence the severity of disease presentation, and thus the need for hospitalization. The variation of IGHG genes from chromosome 14q32 are linked to serum IgG subclass levels but also to the variations in IgG responses to pneumococcal, meningococcal and Haemophilus influenzae antigens. The aim of this investigation was to clarify whether IGHG genes are involved in the development of severe RSV lower respiratory tract infection (LRTI). Methods: The alternative expressions of IGHG3(b) and (g), IGHG I(f) and (a), and IGHG2(n) and (-n) genes were studied in a cohort of 49 previously healthy children hospitalized for RSV LRTI. The gene frequencies were compared to a population of healthy individuals. Results: The homozygous IGHG2(-n/-n) genotypes dominated in hospitalized children with severe RSV infection: 55.1%, compared with 34.2% in the healthy population (OR 2.3; p = 0.004). The IGHG2 genotypes containing (n/n) and (n/-n) were significantly decreased. The IGHG(bf-n) alleles were significantly increased (OR 1.7; p=0.025) and the IGHG(bfn) alleles significantly decreased (OR 0.5; p=0.005). Conclusion: The IGHG(bf-n) allele and homozygous IGHG2(-n/-n) genotypes are associated with the development of severe RSV LRTI.