Introduction
Patients with Down syndrome (DS) are more likely to exhibit immunological abnormalities that predispose them to infection [1-3]. Among other anomalies, individuals with DS have altered serum concentrations of some subclasses of Immunoglobulin G (IgG), particularly the IgG4 subclasses [4]. In line with this, Anneren et al. found low serum IgG4 in 68% of DS patients. This is critical, as Loh et al. found that 90% of DS patients with severe respiratory infection had a low serum IgG4 subclass, while only 25% of healthy DS patients showed such a deficiency [5]. However, the role of low serum IgG4 has not been fully established, as many affected persons in the general population are asymptomatic. For example, one study found that up to 15% of typically developing children and 10% of adults may have an low serum IgG4 [6]. In the context of DS, low serum IgG4 may be an important factor in recurrent infections, the development of autoimmune diseases, and even stroke [7,8]. Despite being the lowest of all IgG subclasses, comprising around 4% of total IgG, IgG4 may play an important role in the body’s mucosal defense because of its relatively higher concentration in external secretions [9]. Low in one or more IgG subclasses can be caused by T cell dysfunction, deletions of the constant region of the heavy chain genes, or abnormalities of isotype switching [10]. Furthermore, in vitro lymphocyte T and lymphocyte B function abnormalities are present in individuals with low IgG levels, suggesting that low IgG subclass levels may be indicative of an underlying lymphocyte B defect, a possible lymphocyte T defect, and significant immunodepression [11,12]. The current literature has not provided a clear consensus on the pathogenic link between low IgG4 and immunoglobulin heavy constant G4 gene (IGHG4 ) in DS. The aim of the present study was to investigate the molecular mechanism of low serum IgG4 at the level of the heavy chain gene (IGHG4 ) in DS.