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Clinical Infectious Diseases 2010;50:672?678
? 2010 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2010/5005-0003$15.00
MAJOR ARTICLE
Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G2 Subclass Deficiency
C. L. Gordon,1
P. D. R. Johnson,1,10
M. Permezel,5
N. E. Holmes,1
G. Gutteridge,2
C. F. McDonald,3
D. P. Eisen,6,10
A. J. Stewardson,6
J. Edington,7
P. G. P. Charles,1
N. Crinis,4
M. J. Black,8
J. Torresi,1,10 and
M. L. Grayson,1,4,9,10
1Infectious Diseases, 2Intensive Care, 3Respiratory, and 4Pathology Departments, Austin Health, 5Department of Obstetrics and Gynaecology, Mercy Hospital for Women, 6Victorian Infectious Diseases Service, Royal Melbourne Hospital, University of Melbourne, Melbourne, 7Intensive Care Unit, Bendigo Health, 8Pathology Department, Alfred Health, 9Department of Epidemiology and Preventive Medicine, Monash University, and 10Department of Medicine, University of Melbourne, Melbourne, Australia
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 ( ), anemia ( ), and low levels of total IgG ( ), IgG1 ( ), and IgG2 (15 of 19 vs 5 of 20; ; mean value ? standard deviation [SD], g/L vs g/L; ) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia ( ) and low mean IgG2 levels ( ) remained significant after multivariate analysis. Follow‐up of 15 (79%) surviving IgG2‐deficient patients at a mean (?SD) of 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 ( ).
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.
? 2010 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2010/5005-0003$15.00
MAJOR ARTICLE
Association between Severe Pandemic 2009 Influenza A (H1N1) Virus Infection and Immunoglobulin G2 Subclass Deficiency
C. L. Gordon,1
P. D. R. Johnson,1,10
M. Permezel,5
N. E. Holmes,1
G. Gutteridge,2
C. F. McDonald,3
D. P. Eisen,6,10
A. J. Stewardson,6
J. Edington,7
P. G. P. Charles,1
N. Crinis,4
M. J. Black,8
J. Torresi,1,10 and
M. L. Grayson,1,4,9,10
1Infectious Diseases, 2Intensive Care, 3Respiratory, and 4Pathology Departments, Austin Health, 5Department of Obstetrics and Gynaecology, Mercy Hospital for Women, 6Victorian Infectious Diseases Service, Royal Melbourne Hospital, University of Melbourne, Melbourne, 7Intensive Care Unit, Bendigo Health, 8Pathology Department, Alfred Health, 9Department of Epidemiology and Preventive Medicine, Monash University, and 10Department of Medicine, University of Melbourne, Melbourne, Australia
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 ( ), anemia ( ), and low levels of total IgG ( ), IgG1 ( ), and IgG2 (15 of 19 vs 5 of 20; ; mean value ? standard deviation [SD], g/L vs g/L; ) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia ( ) and low mean IgG2 levels ( ) remained significant after multivariate analysis. Follow‐up of 15 (79%) surviving IgG2‐deficient patients at a mean (?SD) of 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 ( ).
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.
