Journal Article

Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G<sub>2</sub> Subclass Deficiency

C.L. Gordon, P.D.R. Johnson, M. Permezel, N.E. Holmes, G. Gutteridge, C.F. McDonald, D.P. Eisen, A.J. Stewardson, J. Edington, P.G.P. Charles, N. Crinis, M.J. Black, J. Torresi and M.L. Grayson

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 50, issue 5, pages 672-678
Published in print March 2010 | ISSN: 1058-4838
Published online March 2010 | e-ISSN: 1537-6591 | DOI:
Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G2 Subclass Deficiency

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Severe H1N1 infection appears to be associated with immunoglobulin G2 subclass deficiency in both nonpregnant and pregnant patients. Healthy pregnant women were mildly deficient in immunoglobulin G2, but pregnant women with severe H1N1 infection had lower levels. Immunoglobulin G2 deficiency persisted after recovery in the majority (73%) of cases.

Background. Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G2 (IgG2) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection.

Methods. Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random sample of healthy pregnant women.

Results. Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant; 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P<.001), anemia (P<.001), and low levels of total IgG (P=.01), IgG1 (P=.022), and IgG2 (15 of 19 vs 5 of 20; P=.001; mean value ± standard deviation [SD], 1.8±1.7 g/L vs 3.4±1.4 g/L; P=.003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P=.02) and low mean IgG2 levels (P=.043) remained significant after multivariate analysis. Follow-up of 15 (79%) surviving IgG2-deficient patients at a mean (±SD) of 90±23 days (R, 38–126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG2 deficient. Among 17 healthy pregnant control subjects, mildly low IgG1 and/or IgG2 levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG2 (P=.001).

Conclusions. Severe H1N1 infection is associated with IgG2 deficiency, which appears to persist in a majority of patients. Pregnancy-related reductions in IgG2 level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG2 deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.

Journal Article.  3692 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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