Determinants and Reference Ranges of Serum Immunoglobulins in Middle-Aged and Elderly Individuals: a Population-Based Study

Abstract

Purpose In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges. Methods Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups. Results We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P < .0001 for both). Women had lower IgA (beta: − 0.24; 95% confidence interval [95% CI]: − 0.29; − 0.20) and IgG (beta: − 0.33; 95% CI: − 0.44; − 0.23), but higher IgM levels (beta: 0.08; 95% CI: 0.04;0.13) than men. Former and particularly current smoking were associated with lower IgA and IgG (betas between − 0.07 and − 1.03). Higher alcohol consumption was associated with lower IgG (beta for heavy drinking: − 0.70; 95% CI: − 0.91; − 0.48). Corticosteroid use was associated with lower IgG (beta: − 1.12; 95% CI: − 1.58; − 0.66). Associations with cardiovascular factors were heterogeneous and differed between sexes. Conclusion Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges.

A Direct MS-Based Approach to Profile Human Milk Secretory Immunoglobulin A (IgA1) Reveals Donor-Specific Clonal Repertoires With High Longitudinal Stability

“…In human plasma (i.e., blood from which cells have been depleted) three dominant classes of immunoglobulins are present, namely IgG, IgA and IgM. Their concentration levels differ per individual but are generally highest for IgG 8.3-11.2 g/L, and somewhat lower for IgA 1.6-2.8 g/L and IgM 0.6-1.2 g/L ( 2 ). For human IgG, four sub-classes can be distinguished, IgG1, IgG2, IgG3 and IgG4, and for human IgA two sub-classes co-exist: IgA1 and IgA2.…”

Association between immunoglobulin A and depression in Chinese older adults: findings from a cross-sectional study

“…However, there is little evidence regarding whether immunoglobulin levels are related to depression in older adults. In previous studies, immunoglobulin A levels were lower in Caucasians and showed no significant differences across other ethnicities [ 12 – 14 ]. In addition, data on the associations between immunoglobulins and depression in Asian populations are scarce, especially for Chinese older adults.…”

“…Researchers [ 12 , 13 ] have realized that immunoglobulin A levels were closely associated with age in older adults. Immunoglobulin A levels were found to increase with age in a study involving 8768 participants with a median age of 62 years [ 14 ]. However, there is little evidence regarding whether immunoglobulin levels are related to depression in older adults.…”

Serum Immunoglobulins, Pneumonia Risk, and Lung Function in Middle-Aged and Older Individuals: A Population-Based Cohort Study

“…In a previous study of 39 healthy volunteers, older compared to younger individuals had higher Ig levels in the bronchoalveolar fluid and lower predicted lung function values, although the latter did not reach statistical significance ( 10 ). Recently, we have shown age-related increases of serum IgA and IgG in our general population cohort of middle-aged and older individuals ( 11 ). It is unclear whether an association exists of serum Igs with pneumonia or impaired lung function in this older population.…”