[Deficiency in immunoglobulin subclasses as cause of increased infection susceptibility--a family study]

Within 3 generations 6 members of a family showed diminished serum concentrations of one or more immunoglobulin G (IgG) subclasses. In all 6 individuals IgG-2 levels were low, together with low IgG-3 and/or IgG-4 in 5, but all had normal values for total IgG. The proposita and her 2 children suffered from frequent severe respiratory infections. One child, now aged 11, has had an average of 3 such infections per year since birth, while the other, now aged 8 years, has had 4 episodes annually since birth. Recurrent infection only started at age 34 in the proposita. In these 3 patients a line immuno-binding assay showed diminished subclass-specific IgG-2 antibodies against bacterial polysaccharides. They were replaced by Sandoglobulin, an immunoglobulin for intravenous use. Under substitution by 6 g or 12 g infusions of Sandoglobulin per month no further infections occurred or the infections were clearly milder than before, and the Ig subclass levels became normal. It is concluded that in every case of recurrent respiratory infections of unusual severity suggesting an antibody deficiency, it is advisable to measure not only the total Ig classes (IgG, IgA and IgM) but also the IgG subclasses. The clinical relevance of an Ig subclass deficiency can be further substantiated by measuring subclass-specific antibodies.