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

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. (C) 2008 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 39:18-29