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

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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.

Original languageEnglish
Pages (from-to)1902-1914
Number of pages13
JournalJournal of Clinical Immunology
Volume41
Issue number8
Early online date10 Sept 2021
DOIs
Publication statusPublished - Nov 2021

Bibliographical note

Funding Information:
The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam.

Funding Information:
Virgil A.S.H Dalm received an unrestricted investigator-initiated research grant from Takeda Pharmaceutical Company Limited (IIR-NLD-002671).

Publisher Copyright:
© 2021, The Author(s).

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