Immunoglobulin Levels Investigated in Adults with IgG Subclass Deficiency

Immunoglobulin G (IgG) subclass deficiency (IgGSD) is characterized by frequent or severe upper or lower respiratory tract infection, one or more subnormal IgG subclass level(s) unexplained by other causes, and decreased IgG response to pneumococcal polysaccharide vaccination (PPSV).

IgG subclass deficiency is defined as the decrease of one or more subclasses of IgG antibodies with normal or near normal levels of other immunoglobulin classes. It can present as either as a complete deficiency in instances in which the serum level of a IgG subclass are below detection or as a relative deficiency in which the IgG subclass levels are below normal range for age.


Medical Scientists at the University of Alabama at Birmingham (Birmingham, AL, USA) analyzed data on 207 adults: 39 with subnormal IgG1 only; 53 with combined subnormal IgG1/IgG3; and 115 with subnormal IgG3 only. They compiled data on age; sex; autoimmune condition(s) (AC); atopy; IgG, IgG subclasses, IgA, IgM; IgGsum (IgG1 + IgG2 + IgG3 + IgG4); and D (Δ percentage difference between IgGsum and IgG).

The team compared attributes of patients with/without subnormal IgG (< 7.00 g/L; subnormal IgG1 subclass groups only) and analyzed IgGsum and IgG relationships. IgG at diagnosis in each patient was measured using turbidimetry (Laboratory Corporation of America, Burlington, NC, USA). IgG subclasses were measured using four separate quantifications on corresponding specimens using rate nephelometry (Laboratory Corporation of America), and reported separately from IgG. IgG and IgG subclasses were measured before IgG replacement therapy was initiated.

The investigators reported that there were 39 patients with subnormal IgG1 only (89.7% women), 53 with subnormal IgG1/IgG3 (88.7% women), and 115 with subnormal IgG3 only (91.3% women). Fifteen patients (38.5%) and 32 patients (60.4%) in the respective subnormal IgG1 subclass groups had subnormal IgG. Attributes of patients with/without IgG < 7.00 g/L were similar, except that autoimmune condition prevalence was lower in patients with subnormal IgG1 only and IgG < 7.00 g/L than ≥ 7.00 g/L. Mean/median IgG1 and IgG2 were significantly lower in patients with IgG < 7.00 g/L in both subnormal IgG1 subclass groups. Regression analysis on IgG in three subclass groups revealed positive associations with IgG1 and IgG2.

The authors concluded that both IgG1 and IgG2 are major determinants of IgG in patients with subnormal IgG1, combined subnormal IgG1/IgG3, or subnormal IgG3 and that in patients with subnormal IgG1 or combined subnormal IgG1/IgG3, median IgG2 levels are significantly lower in those with IgG < 7.00 g/L than those with IgG ≥ 7.00 g/L. The study was published on August 9, 2021 in the journal BMC Immunology.

Related Links:
University of Alabama at Birmingham
Laboratory Corporation of America