Infection
Serum Immunoglobulins and Risk of Infection: How Low Can You Go?

https://doi.org/10.1016/j.semarthrit.2008.05.002Get rights and content

Objectives

To determine the relationship between the levels of serum immunoglobulin (Ig) levels and risk of infection. The following 2 main questions are addressed: (1) At what level do reduced serum concentrations of the different Ig species (focusing on IgA, IgG, and IgM) significantly increase the risk of infection above background and (2) For how long can Ig depletion be tolerated before an increased risk of infection becomes apparent.

Methods

Information was gathered from a search of PubMed and relevant congress abstracts up to and including November 2007.

Results

Sustained, very low levels of IgA, IgG, or IgM, as occur in primary immunodeficiency syndromes, are associated with significantly increased risks of infections, primarily respiratory tract infections of bacterial origin. Patients with IgG levels <100 mg/dL or IgM levels <20 mg/dL for prolonged periods have an increased risk of recurrent and sometimes life-threatening infectious episodes. Generally, IgA deficiency appears better tolerated. Replenishment of IgG in patients with hypogammaglobulinemia reduces the infection risk to background if IgG levels are maintained at approximately 500 mg/dL, although higher levels may be necessary in the presence of certain comorbidities. Transient depletion of IgG and/or IgM (or, less commonly, IgA) can occur in some patients following the administration of certain drugs, including anticonvulsants, corticosteroids, and rituximab. Available evidence suggests that such changes are not generally associated with an increased risk of infections.

Conclusions

While prolonged, very low levels of IgG and/or IgM are associated with a heightened risk of infections, transient or less severe immunodeficiency appears to be tolerated in most subjects.

Section snippets

Methods

Information for this article was gathered from a search of the PubMed database between January 1990 and November 2007. The search strategies included [IgA OR IgG OR IgM] AND [deficiency]; [IgA OR IgG OR IgM] AND [infection]; [agammaglobulinemia] OR [hypogammaglobulinemia] AND [infection]; [immunoglobulin] AND [transplantation] AND [infection]; [immunomodulation] AND [immunoglobulin] and were limited to articles in the English language. Relevant publications were hand-searched to identify

Results

Immunoglobulins play 3 critical roles: (1) neutralization of foreign antigens through direct binding; (2) alteration of antigens to a form more readily engulfed by phagocytes; and (3) triggering the release of chemicals to facilitate antigen destruction (3, 4). The immunoglobulin family comprises 5 major classes: immunoglobulin G (IgG); immunoglobulin A (IgA); immunoglobulin M (IgM); immunoglobulin D (IgD); and immunoglobulin E (IgE). Table 1 shows the normal ranges of immunoglobulin levels in

Discussion

Low levels or absence of immunoglobulins in primary and secondary immunodeficiency syndromes are associated with an increased risk of infections, in particular, when immunoglobulin levels remain very low for protracted periods of time. Bacterial infections of the respiratory tract are the most common types of infection seen in these conditions. Deficiency of IgG is most frequently implicated in increased susceptibility to infection. IgA deficiency appears to be less serious in terms of

Acknowledgment

Support for third-party writing assistance for this article, furnished by Neil Anderson, was provided by Genentech, Inc.

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