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

Abstract

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.

Transient low IgG4 levels cause recurrent wheezing requiring multiple hospitalizations in infancy

“…11 Recently, Kim et al showed that there was an association between recurrent wheezing and IgG4 deficiency and demonstrated a significant inverse correlation between wheezing episodes and IgG4 levels in the infantile wheezer group. 14 As in previous reports, our study also found that infants with low IgG4 levels, requiring frequent hospitalizations, may have had severe asthma-like symptoms. We considered that delayed maturation of the immune system in infancy could lead to viral-induced recurrent wheezing and asthma-like symptoms.…”

“…There was a report of which results of intravenous immunoglobulin (IVIG) administration to severe wheezy infants with low level of IgG4 14 . Within 1 week after administration of IVIG, IgG4 increased.…”

Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group

“…The most common IgG1 deficiency results from a generalized deficiency of antibodies, IgG2 deficiency is associated with recurrent viral and bacterial infections, both IgG2 and IgG3 deficiency predisposes to recurrent respiratory tract infections, and IgG4 deficiency has been found in chronic bronchial and lung diseases [ 187 ]. Two studies showed that low levels of the IgG4 subclass were associated with recurrent wheezing, requiring hospitalization in infants and young children [ 188 , 189 ].…”

Human bocavirus respiratory infection: Tracing the path from viral replication and virus‐cell interactions to diagnostic methods

“…75,78 One report found HBoV1 at high frequency in infants with wheezing and low IgA and IgG4 levels, suggesting a possible involvement in recurrent wheezing during childhood. 79 However, the cytokine response in respiratory secretions and peripheral blood has been poorly approached, which encourages further research. In this regard, recent findings indicate that HBoV1 patients hospitalised with ALRI exhibit an increased percentage of cells positive for CD19 and CD23 markers (CD19 þ CD23þ) and a lower proportion of CD3-CD16 þ CD56þ cells, suggesting B-lymphocyte differentiation/activation and decreased NK cell function.…”

“…On the other hand, transient low levels of IgG subclass 4 are associated with recurrent wheezing requiring multiple hospitalisations in childhood and IgA deficiency may predispose to recurrent respiratory infections and wheezing 75,78 . One report found HBoV1 at high frequency in infants with wheezing and low IgA and IgG4 levels, suggesting a possible involvement in recurrent wheezing during childhood 79 . However, the cytokine response in respiratory secretions and peripheral blood has been poorly approached, which encourages further research.…”