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%.