Time-related variation in IgG subclass concentrations in a group of healthy Danish adults.

Introduction: Immunoglobulin G subclass measurements are important for the diagnostic work-up of immunodeficiencies and immunoglobulin G4 (IgG4) related diseases. It is currently unknown whether a single sampling is truly representative for an individual's IgG subclass concentrations. This study aimed to investigate whether IgG and IgG subclass concentrations in healthy individuals are stable over time.

Method: With a span of median 42 weeks, four samples from each of 54 (34M, 20F) healthy adult volunteers (24-66 years) were analyzed for IgG and IgG1-4 using turbidimetry. Concentrations were compared within and between individuals.

Results: IgG and IgG subclass concentrations followed either a normal (IgG, IgG1, and IgG3) or log normal (IgG2 and IgG4) distribution. Immunoglobulin 4 demonstrated by far the widest range of concentrations between individuals (670-fold: 0.004-2.68 g/L). Immunoglobulin G subclass variations within individuals were expressed as pooled standard deviations (PSD). These ranged from 0.056 (IgG4) to 0.955 g/L (IgG) and correlated with mean concentration of IgG or the particular IgG subclass. As a consequence, the relative PSDs (i.e., PSD divided by mean IgG or IgG subclass concentration) fell within a narrow range: 5.82%-10.1%. Based on these numbers, the 95%-upper one-sided confidence limits for intraindividual IgG and IgG subclass variation was calculated to range from 9.82% (IgG2) to 16.9% (IgG4).

Conclusion: The study documents that IgG or IgG subclass concentrations within healthy individuals are very stable over at least 42 weeks. The expected variation for IgG4 concentrations at a 95% confidence level does not exceed ±16.9%.