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.