Low immunoglobulin G4 subclass level is associated with recurrent wheezing in young children

Background: The most important infectious trigger of asthma is the virus and patients with immunoglobulin deficiencies are prone to recurrent respiratory infections. Objective: We investigated the relationship between immunoglobulin G subclass and recurrent respiratory symptom exacerbation and explored possible therapeutic effects of intravenous immunoglobulin administration. Methods: Twenty-eight infants less than 24 months old with 2 or more recurrent wheezing episodes (infantile wheezer group) and 29 asthmatic children aged 24 months to 15 years (bronchial asthma [B-asthma] group) visited our hospital from October 2010 to January 2018. Serum immunoglobulin G, A, M, E, G1, G2, G3, and G4 were measured in each group and compared. In both groups, serum immunoglobulin and symptoms were compared before and after intravenous immunoglobulin administration. Results: The 2 study groups exhibited several statistically significant differences when comparing respiratory virus infection rate (p < 0.001), coinfection rate (p < 0.0001), most commonly found viral infection (human bocavirus vs. human rhinovirus), and immunoglobulin A (p < 0.001), E (p = 0.008), G2 (p < 0.001), and G4 (p = 0.011) levels. In the infantile wheezer group, there was an inverse correlation between immunoglobulin G4 levels and wheezing numbers (R = -0.5538, P = 0.0022). Both groups showed significant changes in immunoglobulin levels and respiratory symptom exacerbations (recurrent wheezing, shortness of breath, chest tightness, cough, and fever) over 1 year after intravenous immunoglobulin administration. Conclusion: There was an association between recurrent wheezing and specific immunoglobulin G deficiencies. We suggest that intravenous immunoglobulin therapy significantly elevates specific immunoglobulin G levels though it lasts only for short term and might be associated with decreased respiratory symptoms. Therefore, low IgG4 levels among infants with recurrent wheezing may be indicative for intravenous immunoglobulin therapy.