Immunoglobulin-G subclass pattern among children with mucopolysaccharidosis attending the genetic clinic of Alexandria University Children’s Hospital

Abstract

Background Mucopolysaccharidosis is an inherited lysosomal-storage disease, due to deficiency in lysosomal enzymes degrading glycosaminoglycans, causing accumulation of undegraded substrate within the lysosomes. These substrates are related to widespread inflammation, as well as the release of various proinflammatory immune mediators and autophagy dysfunction. Oxidative stress, abnormal mitochondrial function, and disruption in homeostasis also play a role in mucopolysaccharide (MPS) pathogenesis. Defects in immunological parameters in MPS have been described and postulated as explanations for the increased severity of infections seen in MPS children. Most of these infections are of the respiratory tract. Aim The aim was to estimate the total level of immunoglobulin G (IgG) and its subclasses in children with MPS and find out the relation if any between the estimated levels and the recurrence of infections. Patients and methods The study was conducted on 35 children with MPS, either newly diagnosed or previously diagnosed cases attending the genetic clinic of Alexandria University Children’s Hospital for follow-up in the period from July 2019 to July 2020. ELISA was used for estimation of the levels of total IgG and its subtypes (IgG1, IgG2, IgG3, and IgG4). Results The levels of total IgG and its subtypes (IgG1, IgG2, IgG3, and IgG4) were measured in all studied cases. A positive significant correlation between IgG3 and repeated upper respiratory-tract infections (URTIs), that 68.2% of cases with high levels of IgG3 had repeated URTIs, while only 31.8% of cases with normal levels of IgG3 had repeated URTIs with P value of 0.001. Conclusion Children with MPS are especially prone to repeated URTIs more than six times/year, this increased susceptibility to infections has been linked to abnormal parameters of the immune system. IgG subclasses are a significant predictor of recurrent URTIs in patients with MPS disease. Therefore, measurement of IgG subclass level, especially IgG3 level, provides a new strategy to more aggressive treatments for high-risk groups.