Immunoglobulin(Ig)G-subclass deficiency (IgGSD) and specific polysaccharide antibody deficiency (SPAD) are two common antibody deficiencies, mainly associated with recurrent respiratory tract infections (RTI). The clinical variability and effect of therapy in a large cohort is not well studied.
A retrospective observational study of children and adults with IgG2SD and/or IgG3SD and/or SPAD and normal total IgG.
In total, 105 patients (age 2y-79y (mean 24y), 53% pediatric, 44% male) were included. To our knowledge, this is the largest cohort of IgGSD and/or SPAD patients studied. Isolated IgG3SD was both in children (16/56;29%) and adults (30/49;61%) most prevalent. Of all IgG2SD(+/-SPAD) cases, 85% were found in children (22/26). In total, isolated SPAD was less frequent (16/105;15%) than IgGSD+SPAD (21/105;20%).
Recurrent upper and lower RTI (76-82% and 38-57% respectively) were most frequently observed, similar in all groups. Gastrointestinal infections (42%;P=0.017) and fatigue (45%;P=0.005) were associated with IgG3SD. Bacterial skin infections (38%;P=0.024) were frequently observed in SPAD. Autoimmunity (25%;P=0.001), lymphadenopathy (71%;P=0.002) and fatigue (59%;P<0.001) were significantly common in adults compared to children. Autoimmunity was not associated with aberrant B-cell maturation, only present in 2.8%. IgG2SD patients (69%;P=0.046) and children (73%;P<0.001) were hospitalized more.
Monocytopenia was repeatedly observed (32/105;30%), predominantly in IgG2SD (15/31;48%) and persistent, without effect of Ig replacement therapy. In patients with Ig replacement, bacterial infection rate reduced significantly in 82%, although low IgG3 persisted.
RTI remain the hallmark presentation in IgGSD and/or SPAD. Our cohort revealed remarkable findings, such as frequent autoimmunity and monocytopenia. Long-term multi-centre studies are needed to better characterize these patients.