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Meta-Analysis
. 2021 Apr 7:12:664526.
doi: 10.3389/fimmu.2021.664526. eCollection 2021.

Determinants of Serum Immunoglobulin Levels: A Systematic Review and Meta-Analysis

Samer R Khan  1   2 , Anna C van der Burgh  1   3 , Robin P Peeters  1   4 , P Martin van Hagen  2   5 , Virgil A S H Dalm  2   5 , Layal Chaker  1   4
Affiliations
Meta-Analysis

Determinants of Serum Immunoglobulin Levels: A Systematic Review and Meta-Analysis

Samer R Khan et al. Front Immunol. .

Abstract

Background: An up-to-date overview of determinants of serum immunoglobulins in adults is pivotal for clinical practice and research, but currently lacking. We therefore performed a systematic review and meta-analysis to identify determinants of serum immunoglobulin levels.

Methods: Embase, Web of Science, Medline, Cochrane, and Google Scholar were searched from inception to July 11th, 2019 for articles reporting on determinants of serum immunoglobulin A, G or M (IgA, IgG or IgM) in adult humans. Random and fixed effect models were applied to obtain pooled mean differences (MDs) and 95% confidence intervals (CIs) for the association of age and sex with serum immunoglobulins.

Results: We retrieved 117 articles reporting on determinants of serum immunoglobulins, of which 28 could be meta-analyzed. Older compared to younger individuals had higher IgA (MD: 0.38; CI: 0.18 - 0.58), but lower IgM levels (MD: -0.40; 95%: -0.66 - -0.14). Men had higher IgA (MD: 0.22; CI: 0.03 - 0.42), but lower IgM levels (MD: -0.21; CI: -0.32 - -0.10) than women. Age and sex did not influence IgG. Caucasian ethnicity was associated with lower IgA, IgG, and IgM. Smoking and corticosteroid use were associated with lower IgG. Positive associations were reported of probiotics with IgG, alcohol with IgA, hypertension with IgA and IgG, and acute psychological stress with IgA, IgG, and IgM.

Conclusions: Older age and male sex are associated with higher IgA, but lower IgM, and urge investigation of age- and sex-specific reference ranges of immunoglobulins. Other identified determinants were ethnicity, diet, lifestyle and cardio-metabolic factors.

Keywords: adult human beings; determinants; meta-analysis; serum immunoglobulins; systematic review.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Forest plots for the association between age and serum immunoglobulin levels. (A) Association of age with serum immunoglobulin A (IgA) (g/l). (B) Association of age with serum immunoglobulin G (IgG) (g/l). (C) Association of age with serum immunoglobulin M (IgM) (g/l). The closed squares with horizontal lines depict the mean differences in serum immunoglobulin levels between older (≥45 years) and young (<45 years) subjects with 95% confidence intervals. The diamonds depict the pooled mean differences between the older and young age groups. The random effect model was taken as primary model.
Figure 2
Figure 2
Forest plots for the association between sex and serum immunoglobulin levels. (A) Association of sex with serum immunoglobulin A (IgA) (g/l). (B) Association of sex with serum immunoglobulin G (IgG) (g/l). (C) Association of sex with serum immunoglobulin M (IgM) (g/l). The closed squares with horizontal lines depict the mean differences in serum immunoglobulin levels between men and women with 95% confidence intervals. The diamonds depict the pooled mean differences between men and women. The random effect model was taken as primary model.
See this image and copyright information in PMC

References

    1. Hoffman W, Lakkis FG, Chalasani G, Cells B. Antibodies, and More. Clin J Am Soc Nephrol (2016) 11:137–54. 10.2215/CJN.09430915 - DOI - PMC - PubMed
    1. Agarwal S, Busse PJ. Innate and adaptive immunosenescence. Ann Allergy Asthma Immunol (2010) 104:183–90; quiz 190-2, 210. 10.1016/j.anai.2009.11.009 - DOI - PubMed
    1. Listi F, Candore G, Modica MA, Russo M, Di Lorenzo G, Esposito-Pellitteri M, et al. A study of serum immunoglobulin levels in elderly persons that provides new insights into B cell immunosenescence. Ann N Y Acad Sci (2006) 1089:487–95. 10.1196/annals.1386.013 - DOI - PubMed
    1. Cassidy JT, Nordby GL, Dodge HJ. Biologic variation of human serum immunoglobulin concentrations: sex-age specific effects. J Chronic Dis (1974) 27:507–16. 10.1016/0021-9681(74)90026-5 - DOI - PubMed
    1. Obiandu C, Okerengwo AA, Dapper DV. Levels of serum immunoglobulins in apparently healthy children and adults in Port Harcourt, Nigeria. Niger J Physiol Sci (2013) 28:23–7. - PubMed

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