Clinical and immunological characterization of IgG subclass deficiency reveals that low levels of pneumococcal antibodies associate with need of immunoglobulin replacement therapy

Abstract Immunoglobulin G subclass deficiencies (IgGsd) comprise a wide clinical spectrum from no symptoms to repeated respiratory infections and risk for the development of lung damage. In Sweden, immunoglobulin replacement therapy (IgRT) is considered in IgGsd patients with a high burden of infections. Our aims were to characterize immunological parameters in IgGsd on and off IgRT, and to identify factors that can predict the need of IgRT in IgGsd. Thirty-five patients with IgGsd were included in this prospective study and followed up to 36 months, when on and off IgRT. We analyzed possible associations between need of continuous IgRT and levels of immunoglobulins, IgG-subclasses, 21 serotype-specific pneumococcal antibodies, complement function and other factors that may predispose for a severe clinical course or increased exposure to airway pathogens. In-depth lymphocyte phenotyping was performed when on and off IgRT and compared to 34 healthy controls. Seventeen of the patients needed continuous IgRT. The prevalence of protective levels of serotype-specific antibodies was lower in IgGsd with need of IgRT. T cell and B cell subsets were similar irrespective of the need of IgRT. A combination of factors including age, autoimmunity, lung disease, fatigue, and a profession associated with increased risk of infections could predict the need of IgRT. In conclusion comorbidities due to dysregulated immunsystem in combination with low IgG subclass levels and presence of low levels of serotype specific IgGs, have a higher impact on the need of IgRT than aberrations in T cell and B cell subsets.