Relevance of circulating IgG levels as a marker of health in plasma donors.

BACKGROUND: Frequent plasma donation is associated with reduced circulating IgG levels, prompting many jurisdictions to apply IgG-based deferral thresholds as a precautionary donor-safety measure. However, whether low IgG in healthy individuals reflects clinically meaningful immunosuppression remains unclear. This study evaluated IgG as a marker for donor health by integrating immunological, behavioral and self-reported outcomes, including vaccine responses, return to donation, and health problems. STUDY DESIGN AND METHODS: The kinetics of IgG decline associated with frequent plasma donation were analyzed over 18 months in 49 first-time and 50 repeat donors. Vaccine responses were evaluated in repeat donors with low or high IgG using ELISA to measure SARS-CoV-2 Spike receptor-binding domain antibodies and avidity after primary and booster COVID-19 vaccination. Return to plasma donation was examined in 3897 first-time plasma donors followed up to 22 months. Self-reported health problems were analyzed in 5347 plasma donors over 10 years. RESULTS: IgG levels declined during early donations in first-time donors but stabilized thereafter, suggesting a new homeostatic set point rather than progressive IgG depletion. All vaccinated donors seroconverted after primary vaccination regardless of IgG level. Although antibody levels were slightly lower in low-IgG donors, affinity maturation was comparable after boosting. IgG levels were not associated with return to donation or increased self-reported health problems. DISCUSSION: Low IgG levels in healthy plasma donors were not associated with impaired immunity, donor retention, or increased self-reported health problems. These findings support cautious interpretation of isolated IgG values in donor management and favor longitudinal monitoring over fixed thresholds.