Selective subnormal IgG3 in 121 adult index patients with frequent or severe bacterial respiratory tract infections

•Autoimmune conditions, atopy, and other allergy manifestations are common.•One-third of patients did not respond to pneumococcal polysaccharide vaccination.•Blood lymphocyte subset levels are normal in most patients.•Subnormal IgG3 is associated with some HLA-A and HLA-B types, haplotypes.•Subnormal IgG3, non-protective S. pneumoniae IgG contribute to infection risk. We characterized 121 adults with frequent or severe bacterial respiratory tract infections at diagnosis of selective subnormal IgG3. Mean age was 47±13 (SD)y; 87.6% were women. Associated disorders included: autoimmune conditions 33.1%; hypothyroidism 14.9%; atopy 29.8%; and other allergy manifestations 41.3%. In 34.1%, proportions of protective Streptococcus pneumoniae serotype-specific IgG levels did not increase after polyvalent pneumococcal polysaccharide vaccination. Blood CD19+, CD3+/CD4+, CD3+/CD8+, and CD56+/CD16+ lymphocyte levels were within reference limits in most patients. In regression analyses, independent variables age; sex; autoimmune conditions; hypothyroidism; atopy; allergy manifestations; corticosteroid therapy; and lymphocyte subsets were not significantly associated with IgG subclass, IgA, or IgM levels. Frequencies of HLA haplotypes A*01, B*08; A*02, B*14; A*02, B*15; A*02, B*44; A*02, B*57; and A*03, B*07 were greater in 80 patients than 751 controls. We conclude that subnormal IgG3 and non-protective S. pneumoniae IgG levels contribute to increased susceptibility to respiratory tract infections.