Calculated globulin as a surrogate marker for hypogammaglobulinemia: establishing clinical decision limits in a Brazilian population cohort

Introduction Inborn errors of immunity (formerly primary immunodeficiencies) encompass a group of genetic disorders characterized by defects in innate and/or adaptive immunity. Serum Immunoglobulin G (IgG) quantification is the diagnostic gold standard for hypogammaglobulinemia, but it is not routinely ordered in general clinical practice. Calculated globulin (CG) has been proposed as a potential surrogate marker. The current study aimed to evaluate the association between CG levels and adverse clinical outcomes and to propose CG-based clinical decision thresholds relevant to a cohort of Brazilian population. Methods A cross-sectional analysis of longitudinal records was conducted encompassing CG measurements from 50, 539 individuals aged ≥1 year. Odds ratios (OR) and probability curves were calculated using predefined CG cut-off points (0.5 to 2.1 g/dL). Results Linear regression analysis demonstrated a linear association between CG and IgG levels, described by the equation IgG = 0.523 × CG − 0.33. Lower CG levels were associated with increased risk of mortality, hospitalization, ICU admission, emergency care utilization, and higher frequency of antibiotic use. A CG threshold of ≤2.0– 2.1 g/dL was associated with a higher risk of adverse outcomes. Discussion CG is a widely available, low-cost parameter with potential utility as a screening tool for primary or secundary antibody deficiencies. Clinical decision thresholds for hypogammaglobulinemia appear to be higher than the lower reference limits currently used in Brazilian laboratories. These findings highlight the need for revised clinical decision limits tailored to specific populations and support the integration of CG into routine screening strategies for earlier detection of antibody deficiencies.